Pubmed abstracts for Protein-Protein Interaction search result :

Interacting proteins: P04626 and P00533	Pubmed	SVM Score :1.4635945
We show that in various cells ErbB 2 can form heterodimers with both EGF receptor ( ErbB 1 ) and NDF receptors ( ErbB 3 and ErbB 4 ) , suggesting that it may affect the action of heterologous ligands without the involvement of a direct ErbB 2 ligand . 1.4635945^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.66866609
Although ErbB 2 binds neither ligand , even in a heterodimeric receptor complex , it is the preferred heterodimer partner of the three other members , and it favors interaction with ErbB 3 . 0.66866609^^^ Whereas ErbB 1 binds to the epidermal growth factor ( EGF ) , both ErbB 3 and ErbB 4 bind to the Neu differentiation factors ( NDFs , or neuregulins ) , and ErbB 2 , the most oncogenic family member , is an orphan receptor whose function is still unknown . 0.63286141^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.70848581
Analysis of a Neu differentiation factor ( NDF ) induced heterodimer between ErbB 3 and ErbB 2 favors a bivalence model ; the ligand simultaneously binds both ErbB 3 and ErbB 2 , but , due to low affinity of the second binding event , ligand bivalence drives dimerization only when the receptors are membrane anchored . 0.70848581^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.54464366
We analyzed the formation of homo and heterodimers between EGFR , ErbB 2 , and ErbB 3 ( members of the EGF receptor family ) in the human skin keratinocyte cell line HaCaT , in dependence of the added ligand . 0.54464366^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.88539444
The mechanism of c erbB 2 gene product increase in stomach cancer cell lines . c erbB 2 oncogene encodes a growth factor receptor whose amino acid sequence has extensive homology with human epidermal growth factor receptor . 0.88539444^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.62250351
Since the c erbB 2 oncogene has extensive structural homology to the epidermal growth factor receptor ( EGFR ) gene , we expect that c erbB 2 oncoprotein would share functional similarities with EGFR leading to both loss of oestrogen receptor and poor prognosis in breast cancer . 0.62250351^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.52267717
RESULTS : There was a direct association of p 53 expression in SCC and mucosa ( p = 0 . 001 ) ; loss of c erbB 2 expression ( ) from normal mucosa to SCC ( p = 0 . 04 ) ; lower frequency of association of c erbB 2 ( + ) with EGFR ( ) in SCC ( p = 0 . 02 ) ; and a direct association of EGFR ( + ) expression in SCC and mitotic index ( p = 0 . 03 ) . 0.52267717^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.94487914
The chimeric E 2 binding gp , called Sindbis SCA erbb 2 , was modified to reduce its native binding function and to contain a single chain antibody ( SCA ) with specificity for the human epidermal growth factor receptor Her2 / neu protein , erbb 2 . 0.94487914^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.52467058
The HER 2 / neu oncoprotein , a 185 kDa membrane associated tyrosine kinase with extensive homology to the epidermal growth factor receptor ( EGF R ) , is overexpressed in breast and ovarian carcinomas . 0.52467058^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.53388415
The Human Epidermal Growth Factor ( HER 2 ) oncogene encodes a transmembrane tyrosine kinase receptor with extensive homology to the Epidermal Growth Factor Receptor ( EGFR ) which is the prototypal member of this family of receptor tyrosine kinases . 0.53388415^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.52280141
Indeed , we find that the experimental data are clearly most consistent with a mechanism in which HER 2 directly competes with EGFR for a stoichiometrically limited quantity of endosomal retention components ( ERCs ) , thereby reducing degradation of ERC coupled EGFR . 0.52280141^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.51125147
Moreover , ErbB 2 was highly phosphorylated in NIH 3T3 cells that coexpress ErbB 2 with either EGFR or ErbB 3 , but not in NIH 3T3 cells that express ErbB 2 alone . 0.51125147^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.72019746
ErbB 2 uses ATP Mg as a substrate inefficiently compared with EGFR and ErbB 4 . 0.72019746^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.8059699
ErbB 2 does not bind ligand , yet appears to be the major signaling partner for other ErbB receptors by forming heteromeric complexes with ErbB 1 , ErbB 3 , or ErbB 4 . 0.8059699^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.88313976
BTC also phosphorylated ErbB 2 at Tyr 877 , Tyr 1112 , and Tyr 1248 and induced association of ErbB 2 with EGFR , suggesting their heterodimerization in VSMCs . 0.88313976^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.68621034
Here we applied a combination of computational modeling and quantitative experimental studies of the dynamic interactions between EGFR and HER 2 and their downstream activation of ERK to understand this complex signaling system . 0.68621034^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.81537957
Since human epidermal growth factor receptor 2 ( HER 2 ) is known to participate with the epidermal growth factor receptor ( EGFR ) in mitogenic signalling , we hypothesised that HER 2 overexpression might indicate responsiveness to EGFR targeted therapies . 0.81537957^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.56816566
Pertuzumab ( rhuMAb 2C4 ) , a humanized HER 2 antibody , represents a new class of targeted therapeutics that inhibit dimerization of HER 2 with ligand activated EGFR ( HER 1 ) , HER 3 , and HER 4 . 0.56816566^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.53921775
Correlation of negative Her 2 / neu protein with negative epidermal growth factor receptor was significant ( p less than 0 . 05 ) in 74 cases . 0.53921775^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.55820689
By performing immunohistochemistry on paraffin embedded tissue sections , we found that ptyr 845 EGFR was significantly co expressed with Her 2 / neu and ptyr 1248 Her 2 / neu ( p=0 . 043 and p=0 . 040 , respectively ) , while ptyr 1173 EGFR was only correlated to Her 2 / neu expression ( p=0 . 042 ) . 0.55820689^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.85026665
Considering the biological significance of an interaction between EGFR and Her 2 / neu signalling in other human malignancies , we have investigated if trastuzumab treatment would affect sEGFR in 33 patients with Her 2 / neu overexpressing metastatic breast cancer . 0.85026665^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.51029891
The NEU proto oncogene encodes a 185 , 000 dalton transmembrane glycoprotein with extensive homology to epidermal growth factor receptor . 0.51029891^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.67919891
The protein product of the rodent neu oncogene , p185neu , is a tyrosine kinase with structural similarity to the epidermal growth factor receptor ( EGFR ) . 0.67919891^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.59311749
Taken together , these observations suggest that activation of c Src by these two closely related EGFR family members results from a direct and specific interaction of c Src with tyrosine phosphorylated Neu . . 0.59311749^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Both epidermal growth factor receptor ( EGFr ) and the oncogene product of c erbB 2 have been shown to be expressed by human malignancies , and in some cases to relate to clinical outcomes . ^^^ Indirect immunoperoxidase staining of 32 freshly frozen surgical specimens revealed an overall expression of EGFr and c erbB 2 of 43 % and 38 % , respectively . ^^^ Correlation of epidermal growth factor receptor and c erbB 2 oncogene product to known prognostic indicators of colorectal cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
EGFR and c erbB 2 protein appeared to have additive effects in reducing the likelihood of response , and none of eight patients with EGFR positive , c erbB 2 positive tumours derived benefit from endocrine therapy . ^^^ The results of this study suggest that c erbB 2 protein overexpression , a marker of poor prognosis in breast cancer , is associated with a lack of response to endocrine therapy on relapse , and particularly in combination with EGFR may be useful in directing therapeutic choices . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The expressions of epidermal growth factors ( EGF ) , epidermal growth factor receptors ( EGFR ) , and the c erbB 2 oncoprotein were immunohistochemically examined in 25 cases of human pancreatic carcinoma and epineoplastic pancreatitis and in 10 non cancerous / non inflammatory pancreatic tissues . ^^^ The positive rates of EGF , EGFR , and the c erbB 2 oncoprotein in cancer tissues were 72 % , 36 % , and 28 % , respectively . ^^^ EGFR and the c erbB 2 oncoprotein were stained mainly on the surfaces of the cancer cells and partly in the cytoplasm . ^^^ In the EGF , EGFR , and c erbB 2 positive cancer tissues , some stromal cells , that is fibroblasts and endothelial cells , were also positive . ^^^ These results suggest that the coexpression of EGF and EGFR and the expression of the c erbB 2 oncoprotein are related to the existence of the invasion of human pancreatic cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunohistochemical studies on oncogene products ( EGF R , c erbB 2 ) and growth factors ( EGF , TGF alpha ) in human breast cancer : their relationship to oestrogen receptor status , histological grade , mitotic index and nodal status . ^^^ In this investigation , 83 human mammary carcinomas were examined for the expression of oestrogen receptor ( ER ) , epidermal growth factor receptor ( EGF R ) , epidermal growth factor ( EGF ) , transforming growth factor alpha ( TGF alpha ) , c erbB 2 , histological grade , mitotic index and nodal status , all of which are reportedly prognostically significant factors ( Bloom and Richardson 1957 ; Baak et al . 1985 ; Wright et al . 1989 ) . ^^^ ER expression was biochemically recognized in 43 . 4 % of mammary carcinomas , and EGF R , EGF , TGF alpha and c erbB 2 were histochemically recognized in 25 . 3 , 14 . 5 , 27 . 7 and 18 . 0 % of mammary carcinomas examined respectively , using conventional sections of buffered formalin fixed , paraffin embedded tissue and monoclonal or polyclonal antibodies . ^^^ There were significant relationships between negative ER and positive EGF R or TGF alpha ; positive EGF R and TGF alpha ; positive EGF R and c erbB 2 ; and positive c erbB 2 and TGF alpha . ^^^ Therefore , the present investigation indicates that the negative ER , single expression of c erbB 2 and co expression of EGF R and TGF alpha are important markers which contribute indirectly to prognosis , which reconfirms previous findings on the former two while adding the new finding that immunohistochemical demonstration of expression of EGF R and TGF alpha may provide useful information for selecting the appropriate treatment . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The epidermal growth factor receptor and the c erbB 2 protein are members of the erbB family and are good examples of genes that appear to act through this mechanism . ^^^ Identification and interpretation of epidermal growth factor and c erbB 2 overexpression . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
HER 2 ( also called c erbB 2 or neu ) is a member of the EGFR family whose natural ligand is still unknown . ^^^ Heterodimerization of c erbB 2 with different epidermal growth factor receptor mutants elicits stimulatory or inhibitory responses . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Abnormalities of epidermal growth factor receptor ( EGFR ) and c erbB 2 have been demonstrated to be correlated with aggressive biologic behavior in a variety of human cancers . ^^^ To analyze the possible roles of these oncogenes in ovarian neoplasms , immunolocalization of EGFR and c erbB 2 oncogene product was performed in 45 cases of human ovarian mucinous and serous cystadenomas , carcinomas of low malignant potential ( LMP ) , and invasive carcinomas by employing antibodies against these oncogene products . ^^^ These results indicate that EGFR may be involved in the neoplastic process in epithelial ovarian adenocarcinoma , especially mucinous carcinoma , but involvement of c erbB 2 is probably not as prevalent as considered previously . ^^^ Immunolocalization of epidermal growth factor receptor and c erbB 2 oncogene product in human ovarian carcinoma . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We find that differential PCR is able to detect amplification of the HER 2 ( c erbB 2 ) and the epidermal growth factor receptor ( EGFR ) genes and can be used to arrive at a semiquantitative estimate of gene dosage . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Preliminary study on oncogene product immunohistochemistry ( c erbB 2 , c myc , ras p 21 , EGFR ) in breast pathology . ^^^ The expression of oncogene products related to cell growth ( c erbB 2 , c myc , ras p 21 , EGFR ) was investigated in benign ( 15 cases ) and malignant breast lesions ( 20 cases ) by means of immunohistochemistry using the avidin biotin peroxidase technique with polyclonal and monoclonal antibodies . ^^^ In breast cancer we studied the distribution of immunohistochemical positivity for EGFR , c erbB 2 , c myc , ras p 21 and Ki 67 , which was related to age , nodal status , ER and PgR receptor status , LI , DI and histopathological grading . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
No correlation was observed between the amplified c erbB 2 oncogene and the epidermal growth factor receptor ( EGFR ) . . ^^^ C erbB 2 oncogene amplification in breast cancer in correlation to steroid and epidermal growth factor receptor ] . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The expression of p 53 protein , oestrogen receptor protein , epidermal growth factor receptor ( EGFR ) and overexpression of the c erbB 2 oncoprotein was examined in a series of 149 primary symptomatic breast carcinomas . ^^^ Statistical associations of tumour oestrogen receptor positivity and lack of p 53 protein expression , chi 2 = 19 . 78 ( d . f . = 1 ) , P less than 0 . 001 , positive tumour p 53 status and poor tumour grade ; chi 2 = 14 . 1 ( d . f . = 2 ) , P less than 0 . 001 , EGFR expression chi 2 = 7 . 07 , ( d . f . = 1 ) , P less than 0 . 01 and tumour c erbB 2 protein overexpression ; chi 2 = 4 . 61 ( d . f . = 1 ) , P = 0 . 032 were identified . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The expression of c erbB 2 oncoprotein and epidermal growth factor receptor ( EGFR ) was examined by immunocytochemical and radioreceptor assays in 115 patients with primary breast cancer . ^^^ In 48 of 115 patients ( 42 % ) , the assays were found to be positive for the expression of c erbB 2 oncoprotein , and , in 44 of 115 ( 35 % ) patients , the assays were positive for the expression of EGFR . ^^^ There was no correlation between the expression of c erbB 2 oncoprotein and EGFR . ^^^ Clinical survey demonstrated that both c erbB 2 oncoprotein expression and EGFR expression have independent prognostic values . ^^^ Furthermore , when patients were divided into three groups on the basis of the expression of both c erbB 2 oncoprotein and EGFR , those who were found to be positive for the expression of both c erbB 2 oncoprotein and EGFR showed a worse prognosis than other groups . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The c erbB 2 ( HER 2 / neu ) protein is a membrane glycoprotein growth factor receptor showing molecular homology with the epidermal growth factor receptor ( EGFR ) . ^^^ Normal surface ovarian epithelium was weakly positive for both c erbB 2 protein and EGFR . ^^^ In surface inclusion cysts , however , the epithelial cells lining the lumen exhibited stronger staining for c erbB 2 protein , but no staining for EGFR . ^^^ All 16 benign ovarian tumours and the 2 borderline malignant ovarian tumours were positive for c erbB 2 protein and negative for EGFR . ^^^ Of the ovarian carcinomas , 13 of the 19 ( 68 . 4 % ) were positive for c erbB 2 protein and negative for EGFR , while 4 showed positivity for both c erbB 2 protein and EGFR . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We conducted a trial in 42 benign and malignant meningiomas to assess a possible influence of preoperative dexamethasone therapy on mitotic index , labelling indices of proliferating cell nuclear antigen ( PCNA ) , progesterone receptor , epidermal growth factor receptor ( EGF R ) , c erbB 2 oncoprotein , cathepsin D , gamma gamma enolase as well as the mean number of silver stained nucleolar organizer region associated proteins ( AgNORs ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We analyzed the alteration of int 2 , c erbB 2 and EGFR genes in 32 cases of transitional cell carcinoma of the urinary tract , 15 cases of renal cell carcinoma and 14 cases of prostatic carcinoma by Southern blot hybridization method . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Several oncoproteins ( c myc , c Ha ras , c erbB 2 ) and growth factors / receptors ( EGF , EGF R , TGF alpha ) were immunostained . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunohistochemical staining for epidermal growth factor , epidermal growth factor receptor , or c erbB 2 protein was negative . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : A study was undertaken to define the prognostic value of the expression of the c erbB 2 oncoprotein in a series of breast cancer patients when compared by multivariate analysis with expression of the epidermal growth factor receptor ( EGFR ) , DNA ploidy , and conventional clinicopathologic features . ^^^ Overexpression of the c erbB 2 oncoprotein was poorly associated with EGFR expression and the conventional pathologic features , and it was weakly associated with DNA ploidy and nodal status . ^^^ Univariate analysis showed that c erbB 2 expression , nodal status , DNA ploidy , and EGFR provided significant prognostic information concerning 4 year relapse free survival ( RFS ) with the odds ratios ( ORs ) of not relapsing of 2 . 94 , 2 . 83 , 2 . 34 , and 2 . 20 , respectively . ^^^ Human breast cancer : prognostic significance of the c erbB 2 oncoprotein compared with epidermal growth factor receptor , DNA ploidy , and conventional pathologic features . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Expression of the p 53 , the epidermal growth factor receptor ( c erbB 1 ) and c erbB 2 protein was studied in 34 men with benign prostatic hyperplasia and 29 men with locally advanced prostate cancer by means of an immuno histochemical method . ^^^ On the other hand , the epithelium in benign glands was stained positively for c erbB 2 in 18 % ( 6 / 34 ) and for the epidermal growth factor receptor in 88 % ( 30 / 34 ) ; whereas malignant epithelium stained strongly for c erbB 2 in 21 % ( 6 / 29 ) and for the epidermal growth factor receptor in only 17 % ( 5 / 29 ) . ^^^ Most of the tumours were advanced and no significant relationship was observed between tumour stage and grade and expression of p 53 , the epidermal growth factor receptor or c erbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The c erbB 2 ( HER 2 / neu ) protein is a membrane glycoprotein growth factor receptor that has molecular homology with the epidermal growth factor receptor ( EGFR ) . ^^^ To investigate the relationship between the expression of c erbB 2 protein and EGFR in the tissues of the human female genital tract and in the placenta , we examined the immunohistochemical reactivity of monoclonal antibodies against both of these proteins . ^^^ In the mllerian derived genital tract , epithelial cells of the fallopian tube , endometrium , and endocervix showed reactivity for c erbB 2 protein , whereas reactivity for EGFR was distributed mainly in the stromal cells throughout the menstrual cycle and during pregnancy . ^^^ In the exocervical squamous epithelium , basal cells were c erbB 2 protein negative and EGFR positive , but the more differentiated squamous cells of the intermediate layer were c erbB 2 protein positive and EGFR negative . ^^^ In the placental tissues , cytotrophoblasts and syncytiotrophoblasts of the chorionic villi were c erbB 2 protein negative and EGFR positive . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The c erbB 2 proto oncogene encodes a transmembrane protein which is homologous to the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Epidermal growth factor receptor , platelet derived growth factor receptor , and c erbB 2 receptor activation all promote growth but have distinctive effects upon mouse mammary epithelial cell differentiation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Additionally , the labeling indices of mucosal epithelial cells and chondroblasts also exhibited variable patterns which were associated with a cyclic pattern of expression of c fos and c erbB 2 proto oncogenes and epidermal growth factor receptor . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Class switched monoclonal antibody SV 2 61r recognized the extracellular domain of c erbB 2 protooncogene products separate from the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Comparison of EGFR , c erbB 2 product and ras p 21 immunohistochemistry as prognostic markers in primary breast cancer . ^^^ In a prospective study of 75 breast carcinomas , monoclonal antibodies EGFR 1 , Anti serum 21N ( As21N ) and RAP 5 were used to assess immunohistochemically expression of Epidermal Growth Factor Receptor ( EGFR ) , c erbB 2 oncoprotein and ras protein p 21 . ^^^ C erbB 2 and ras expression both correlated with ER levels and EGFR , but not with the Prognostic Index . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Sera from mice with c erbB 2 negative tumors or tumors overexpressing the epidermal growth factor receptor were negative in the assay . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The c erbB 2 ( neu ) gene encodes a transmembrane phosphoglycoprotein ( p185erbB 2 ) which resembles a growth factor receptor like molecule closely related to the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
There was no significant correlation between expression of c erbB 2 oncoprotein and conventional prognostic factors , estrogen receptor ( ER ) , axillary lymph node metastasis and epidermal growth factor receptor ( EGFR ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In this review 1 summarize the experimental data in favor of the notion that control of epidermal growth factor ( EGF ) receptor ( R ) and / or c erbB 2 protooncogene expression by specific autocrine growth factors and certain classical endocrine hormones serves as a transducer of extracellular signals that ultimately lead to growth responses in breast carcinoma cells . 1 summarize some new results on the role of epidermal growth factor ( EGF ) , transforming growth factor ( TGF ) alpha , and TGF beta in the control of EGF R protooncogene expression in human breast carcinoma cells . ^^^ Furthermore , the data embracing the hypothesis that the growth actions of hormone receptors that are homologous to the 5 erbA oncogene ( estrogens , progesterone , thyroid hormones , retinoic acid , and vitamin D ) are mediated , in part , by modulating EGF R and / or c erbB 2 protooncogene transcription are reviewed . ^^^ Finally , 1 develop the theme that cooperation of certain c erb A related , c erbB 2 and / or EGF R gene products contribute to the uncontrolled growth of human mammary carcinoma cells . ^^^ From the evidence reviewed , one can infer that elucidation of the molecular control of EGF R / c erbB 2 gene expression by c erbA related gene products may lead to both a better understanding of breast carcinogenesis and a new therapeutic approach directed at controlling the transcriptional responses of EGF R / c erbB 2 genes . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Using immunohistochemical methods , the expression of c erbB 2 oncoprotein , epidermal growth factor receptor ( EGFR ) and cathepsin D were compared in the two groups . ^^^ A similar proportion of screened and unscreened tumours expressed c erbB 2 oncoprotein and EGFR but expression of the oestrogen regulated protein cathepsin D was significantly more frequent in the screened group ( P less than 0 . 05 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
A novel multiparameter flow cytometric method was used to quantify the expression of epidermal growth factor receptor ( EGFR ) and c erbB 2 oncoprotein on 85 cryopreserved normal tissues ( 30 ovary , 29 endometrium , 16 cervix ) and 67 carcinomas ( 31 ovarian , 18 cervical , 15 endometrial , 3 vulvar ) . ^^^ Overexpression of the EGFR and c erbB 2 oncoproteins was found in respectively 3 / 31 ( 9 % ) and 10 / 31 ( 32 % ) ovarian carcinomas , 13 / 18 ( 72 % ) and 7 / 18 ( 38 % ) cervical carcinomas , and 2 / 15 ( 13 % ) and 2 / 15 ( 13 % ) endometrial carcinomas . ^^^ Aneuploid tumors expressed levels of EGFR and c erbB 2 oncoprotein significantly higher than those of DNA diploid tumors ( P = 0 . 042 and P = 0 . 048 , respectively ) . ^^^ Oncoprotein could be detected in nearly all normal tissues : expression was higher in premenopausal than in postmenopausal patients ( EGFR , P = 0 . 07 ; c erbB 2 , P less than 0 . 001 ) . ^^^ The present study supports the idea that EGFR and c erbB 2 may play an important role in the autocrine , paracrine , and / or endocrine growth control and differentiation of normal tissues . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Monoclonal antibodies to myc , c erbB 2 and epidermal growth factor receptor ( EGF R ) were raised using a synthetic peptide approach . ^^^ All of the monoclonal antibodies detected peptide blockable bands of appropriate molecular weight ( myc p62 / 66 kDa , c erbB 2 185kDa ; EGF R 150 / 170 kDa ) on immunoblots . ^^^ The monoclonal antibodies to c erbB 2 and EGF R immunostained subpopulations of tumour cells on sections of formalin fixed , paraffin wax embedded human infiltrating and invasive ductal carcinomas of breast . ^^^ The production and characterisation of monoclonal antibodies to myc , c erbB 2 and EFG receptor using a synthetic peptide approach . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
HER 2 or c erbB 2 is a putative growth factor receptor with sequence homology to the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Expression of the p 53 , the epidermal growth factor receptor ( EGFr ; c erbB 1 ) and c erbB 2 proteins was studied in 82 patients with primary transitional cell carcinoma of the bladder using an immuno histochemical method . ^^^ Strong staining was found in 15 % of tumours for c erbB 2 and in 31 % for the EGFr . ^^^ Expression of mutant p 53 , c erbB 2 and the epidermal growth factor receptor in transitional cell carcinoma of the human urinary bladder . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Since the c erbB 2 protein appears to be the receptor of an as yet unidentified growth factor , epidermal growth factor receptor ( EGFR ) was used as a control of a ligand dependent receptor . ^^^ On the contrary , the active c erbB 2 protein , in which Val 659 was replaced by Glu in the transmembrane domain , and EGF stimulated EGFR showed significant levels of tyrosine phosphorylation in vivo . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Epidermal growth factor receptors ( EGFr ) and oestrogen receptors ( ER ) measured by ligand binding , c erbB 2 expression assessed by immunochemistry and lymph node status were compared with p 53 staining . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Thirty specimens of human endometrial carcinoma ( n = 23 ) and cervical adenocarcinoma ( n = 7 ) have been analyzed for c myc , epidermal growth factor receptor ( EGFR ) and c erbB 2 by immunohistochemistry . ^^^ In endometrial carcinomas , expression of c myc was observed in all cases , EGFR in 21 of 23 cases ( 91 . 3 % ) and c erbB 2 in 7 of 23 cases ( 30 . 4 % ) . ^^^ In cervical adenocarcinomas , expression of c myc was seen in 5 of 7 cases ( 71 . 6 % ) , EGFR in all cases and c erbB 2 in 2 of 7 cases ( 28 . 6 % ) . c myc immunoactivity was observed as nuclear or cytoplasmic stain or both , EGFR as membrane and cytoplasmic stain , c erbB 2 as membrane stain . ^^^ Expression of c myc , epidermal growth factor receptor and c erbB 2 in human endometrial carcinoma and cervical adenocarcinoma . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The Mr 185 , 000 glycoprotein encoded by human c erbB 2 / neu / HER2 gene , termed c erbB 2 gene product , shows a close structural similarity with epidermal growth factor receptor and is now regarded to be a growth factor receptor for an as yet unidentified ligand . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The epidermal growth factor receptor ( EGFR ) and the protein products of c erbB 2 and c met proto oncogenes belong to a family of growth factor receptors with tyrosine kinase activity . ^^^ In human colonic carcinomas , the expression of the EGFR and c erbB 2 have been studied at the protein level only , while c met expression has not been reported . ^^^ The results demonstrate that the normal mucosa shows highly variable levels of EGFR and c erbB 2 mRNAs , but expresses consistently low amounts of c met mRNA . ^^^ Colorectal carcinomas did not express significantly higher levels of the EGFR and c erbB 2 mRNAs than the normal mucosa . ^^^ Overexpression of c met proto oncogene but not epidermal growth factor receptor or c erbB 2 in primary human colorectal carcinomas . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Over expression of the Epidermal Growth Factor receptor ( EGF r ) and the c erbB 2 oncogene were not correlated with Ki 67 staining . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
These are dbpB , a DNA binding protein of unknown specificity which binds to the epidermal growth factor receptor enhancer and c erbB 2 gene promoter ( Sakura , H . , Maekawa , T . , Imamoto , F . , Yasuda , K . , and Ishii , S . ( 1988 ) Gene ( Amst . ) 73 , 499 507 ) , and YB 1 , a protein which recognizes the Y box ( inverted CCAAT motif ) of the HLA DR alpha chain gene ( Didier , D . ^^^ EFIA / dbpB / YB 1 share a highly conserved region of 100 amino acids with dbpA , another protein identified by Sakura et al . ( 1988 ) which binds to the epidermal growth factor receptor enhancer and c erbB 2 gene promoter , and with two Xenopus CCAAT binding proteins , FRG Y 1 and FRG Y 2 ( Tafuri , S . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In situ distribution of oncogene products and growth factor receptors in breast carcinoma : c erbB 2 oncoprotein , EGFr , and PDGFr beta subunit . ^^^ The aims of the present study were to determine how three of these receptors , c erbB 2 protein , epidermal growth factor receptor ( EGFr ) and the beta subunit of platelet derived growth factor receptor ( PDGFr beta subunit ) , can effectively be demonstrated by immunohistochemical methods in breast tumors , how these receptors are distributed at the cellular level and how their expression correlates with well established prognostic indicators including hormone receptors and proliferative index . ^^^ We examined frozen tissue sections of 50 invasive human breast carcinomas , including 45 ductal , four lobular , and one mucinous tumours , by immunocytochemical methods to determine the in situ distributions of c erbB 2 , EGFr , and PDGFr beta subunit . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The role of the epidermal growth factor receptor and the c erbB 2 protein in breast cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Expression of the product of the c erbB 2 gene , a proto oncogene related to , but distinct from c erbB 1 encoding the epidermal growth factor receptor ( EGF R ) , was investigated in human urinary bladder carcinomas . ^^^ Immunohistochemical analysis of c erbB 2 oncogene product and epidermal growth factor receptor expression in human urinary bladder carcinomas . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Expression of the c erbB 2 gene product and the epidermal growth factor receptor ( EGF R ) was investigated in 54 cases of human bladder cancer immunohistologically and by Western blot analysis . ^^^ The expression of EGF R was independent of histological grading , tumor stage , and nodal status , and no correlation was observed between expression of the c erbB 2 product and EGF R . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
A series of molecular changes are now known to be seen in human pancreatic neoplasia , including the very frequent mutational activation of Kirsten ras oncogene at codon 12 , overexpression of the epidermal growth factor receptor , and abnormalities of c erbB 2 expression . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
No evidence was found for amplification or overexpression of the c erbB 2 or EGFR genes in any tumor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
As factors regulating growth and differentiation of cervical squamous epithelium , immunohistochemical expression of estrogen receptor ( ER ) , progesterone receptor ( PR ) , epidermal growth factor receptor ( EGFR ) , c erbB 2 protein , adult T cell leukemia derived factor ( ADF ) , and HPV DNA was examined . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Other genes ( c myc , c erbB 2 , c fos and epidermal growth factor receptor ) were also studied . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Epidermal growth factor receptor , but not c erbB 2 , activation prevents lactogenic hormone induction of the beta casein gene in mouse mammary epithelial cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The c erbB 2 gene is a 5 erbB related proto oncogene which is distinct from the gene encoding the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Western blotting failed to detect c erbB 2 in normal fetal tissues but did confirm expression in a microvillous membrane preparation of placenta . c erbB 2 expression is widespread in the human fetus and occurs at an earlier stage than epidermal growth factor receptor . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunohistochemical studies on oncogene products ( c erbB 2 , EGFR , c myc ) and estrogen receptor in benign and malignant breast lesions . ^^^ This study was aimed at elucidating the immunohistochemical localization of oncogene products which are related to cell growth , c erbB 2 product , epidermal growth factor receptor ( EGFR ) , c myc protein and estrogen receptor ( ER ) , in benign and malignant lesions of the breast . ^^^ C erbB 2 product and EGFR were localized on the cell membrane whereas c myc protein and ER were observed in the nuclei . ^^^ In breast cancers , the incidence of immunoreactivity for c erbB 2 was higher in the cases with lymph node metastasis than cases without nodal metastasis ( p less than 0 . 05 ) and there was reciprocal correlation between the expressions of EGFR and ER ( p less than 0 . 05 ) . ^^^ Regarding the size of the primary tumour , there was no statistically significant correlation with the expressions of c erbB 2 , EGFR , c myc or ER . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Amplification of c erbB 2 oncogene in human adenocarcinomas in vivo . ^^^ There are two genes related to the viral erbB gene in the human genome . c erbB 1 is the same as the gene for the epithelial growth factor ( EGF ) receptor , and c erbB 2 encodes a receptor like protein very similar to , but distinct from , the EGF receptor . ^^^ Hybridisation analysis of DNA from 101 fresh human malignant tumours showed that the c erbB 2 gene was amplified in 5 of 63 adenocarcinomas and none of 38 other types of tumours , whereas the c erbB 1 / EGF receptor gene was amplified only in 1 of 8 squamous cell carcinomas . ^^^ Thus , the protein products of the amplified c erbB 2 gene may have a role in the evolution of adenocarcinomas , as does the EGF receptor in some squamous cell carcinomas . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
These data indicate that the promoter of the human c erbB 2 protooncogene is different from that of the protooncogene c erbB 1 ( epidermal growth factor receptor gene ) , which does not contain either a TATA box or a CAAT box . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We were also able to identify the c erbB 2 gene that seems to code for a EGF receptor like protein with a domain for tyrosine kinase . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
A 5 erbB related protooncogene , c erbB 2 , is distinct from the c erbB 1 / epidermal growth factor receptor gene and is amplified in a human salivary gland adenocarcinoma . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunohistochemical localization of transforming growth factor alpha , epidermal growth factor receptor and c erbB 2 protein in hyperplastic human prostates . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The value of tumor angiogenesis , EGFR and c erbB 2 oncoprotein , a long with p 53 protein expression for predicting relapse free survival was investigated in 110 node negative breast cancer patients . ^^^ EGFR , c erbB 2 oncoprotein and p 53 oncoprotein were also determined by immunocytochemical assay . ^^^ Univariate analysis showed no statistical significance of EGFR , c erbB 2 and p 53 status as a prognostic indicator . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Quantification of oestrogen receptor ( ER ) , epidermal growth factor receptor ( EGFR ) , c erbB 2 receptor levels and ploidy were examined on the total and cytokeratin positive cell populations . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
No such association was observed between either c erbB 2 or epidermal growth factor receptor ( EGFR ) expression in the original tumours and their in vivo tumour take . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Specimens of the primary carcinoma were available for analysis of hormone receptor , Ki 67 labelling index , epidermal growth factor receptor ( EGFR ) , c erbB 2 , p 53 and ras p 21 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunohistochemical expression of EGF R , c erbB 2 and c erbB 3 , members of the type 1 family of receptor tyrosine kinases , were investigated in 67 primary ovarian tumour samples ( 46 malignant , 8 borderline and 13 benign ) , and related to tumour clinicopathological features . ^^^ No significant correlations were observed between either EGF R or c erbB 3 and clinical parameters such as tumour stage , differentiation or extent of debulking surgery , but c erbB 2 was significantly associated with several indicators of prognosis , including early stage and good / moderate differentiation in optimally debulked tumours . ^^^ Co expression of EGF R with c erbB 2 , and c erbB 2 with c erbB 3 was significantly greater in malignant tumours than in borderline or benign tumours , and within the malignant tumour group , positive associations were observed between EGF R and c erbB 3 , also between c erbB 2 and c erbB 3 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Twenty one invasive squamous cell carcinomas ( SCC ) of the bladder from Schistosoma hematobium infected patients were examined immunohistochemically for the expression of p 53 , Rb , EGFR and c erbB 2 proteins ; and screened by single strand conformation polymorphism and sequencing for mutations in the ras ( H , N , K ) codon hotspots ( 12 , 13 , 61 ) and p 53 ( exons 4 9 ) genes . ^^^ Positive staining for p 53 , EGFR and c erbB 2 was reported in 38 , 67 and 28 % of tumors respectively . ^^^ The frequency of detection of over expression of EGFR and c erbB 2 in bilharzial bladder lesions is comparable to that reported in TCC , contrasting with the infrequent loss of Rb expression found in invasive lesions associated with schistosomiasis infection . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ER negativity was significantly correlated with the expression of p 53 , epidermal growth factor receptor ( EGFR ) and c erbB 2 ( p < 0 . 05 each ) . ^^^ Thus , it was concluded that ER positive breast carcinomas , relatively small in size , preferentially expressed HSP 27 , HSP 70 and pS 2 and that ER negative tumors , relatively large in size , were predisposed to express p 53 , EGFR and c erbB 2 . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The expression of Cath D , c erbB 2 and EGFR in breast cancer and its correlation to lymphatic metastasis ] . ^^^ The expression of Cath D c erbB 2 and EGFR in breast cancer and its correlation of lymphatic metastases were studied in 277 cases by immunohistochemical technique . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In the present study , the c erbB 2 gene product was shown by far Western blotting analysis to associate directly with both beta catenin and plakoglobin through its cytoplasmic domain core region , which showed extensive homology with epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In the case of c erbB 1 ( epidermal growth factor receptor ) and c erbB 2 , this has been closely linked with poor prognosis , and in particular is apparently associated with an invasive / metastatic phenotype and relative insensitivity to conventional therapies . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunohistochemical study of PCNA , EGFR , c erbB 2 and p 53 in carcinomas of large intestine ] . ^^^ Immunohistochemical stainings for EGFR , c erbB 2 , p 53 and PCNA were performed on 36 and 30 cases of intramucosal and advanced carcinomas of large intestine . ^^^ Positive rate was 58 . 3 % , 41 . 6 % , 58 . 3 % and 60 . 6 % for EGFR , c erbB 2 , p 53 and PCNA in the intramucosal cases , and 66 . 7 % , 50 % , 66 . 7 % and 72 . 6 % in the advanced ones , respectively . ^^^ It seemed likely that relationship between p 53 and c erbB 2 was more significant than that between p 53 and EGFR . ^^^ Positive rate of PCNA was of intimate relationship among that of EGFR , c erbB 2 and p 53 , and the positive rate increased in the advanced carcinomas . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Nevertheless , few reports suggest that c erbB 2 / neu , which is a prognostic marker in breast cancer , epidermal growth factor receptor ( EGFR ) , which is overexpressed in a variety of neoplasms , and fibroblast growth factor 3 ( FGF 3 / INT 2 ) , which has been found to be amplified in breast and ovarian cancer , could be implicated in the development of endometrial adenocarcinoma . ^^^ Amplification of c erbB 2 / neu , EGFR , and FGF 3 / INT 2 was examined in 50 endometrial carcinomas , 10 adenomatous hyperplasias , and 50 normal endometrial samples , using the genomic differential polymerase chain reaction with the single copy reference gene interferon gamma . ^^^ CONCLUSION . c erbB 2 / neu but not EGFR gene amplification was detected and FGF 3 / INT 2 amplification and advanced disease were correlated in endometrial cancer . . ^^^ Detection of c erbB 2 / neu and fibroblast growth factor 3 / INT 2 but not epidermal growth factor receptor gene amplification in endometrial cancer by differential polymerase chain reaction . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Combined overexpression of c erbB 2 protein and epidermal growth factor receptor ( EGF R ) could be predictive of early and long term outcome in human breast cancer : a pilot study . ^^^ In order to determine the prognostic value of c erbB 2 protein and Epidermal Growth Factor Receptor ( EGF R ) , we used an immunohistochemical procedure with specific antibodies on paraffin embedded material from a series of 73 operable breast cancer carcinomas . c erbB 2 protein ( c erbB 2 score > 1 ) was overexpressed in 10 / 73 cases ( 14 % ) and EGF R ( EGF R ratio > 1 ) in 42 / 73 cases ( 58 % ) . c erbB 2 overexpression was correlated with tumour size ( P < 0 . 02 ) and lymph node involvement ( P = 0 . 05 ) whereas EGF R overexpression did not correlate with any of the variables tested . ^^^ The relative risk of relapse was respectively 1 vs 4 . 5 ( P = 0 . 001 ) for patients with a negative ( 0 1 ) or positive ( > 1 ) c erbB 2 score and 1 vs 3 for patients with an EGF R ratio < or = 1 and > 1 ( P = 0 . 03 ) . ^^^ Moreover , c erbB 2 protein overexpression is more specifically an early factor of poor prognosis whereas EGF R overexpression is a long term factor of poor prognosis . ^^^ Patients with an early good prognosis ( c erbB 2 score = 0 1 ) are found to relapse with time when EGF R is overexpressed . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Gene amplification for c erbB 2 , c myc , epidermal growth factor receptor , int 2 , and N myc measured by quantitative PCR with a multiple competitor template . ^^^ To increase the number of assayable oncogenes and the accuracy of the quantitative comparison of gene amplification degree within the same tumor , we have now constructed a single synthetic competitor for int 2 , c myc , N myc epidermal growth factor receptor , and c erbB 2 genes , and for the reference gene beta globin . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Gene expression of growth factors including epidermal growth factor ( EGF ) , transforming growth factor alpha ( TGF alpha ) , epidermal growth factor receptor ( EGFR ) , oncogenes such as c myc , N ras , c erbB 2 and tumor suppressor gene P 53 were studied in 4 human lung cancer cell lines using Northern blot technique . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The expressions of c erbB 2 oncogene and epidermal growth factor receptor ( EGFR ) were investigated immunohistochemically in specimens from 184 cases of hepatitis B , cirrhosis and hepatocellular carcinoma ( HCC ) and 29 normal liver specimens . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Primary and metastatic ovarian cystadenocarcinomas , carcinomas of low malignant potential ( borderline tumors ) , benign ovarian cystadenomas , and normal ovaries were compared for immunoperoxidase detection of the ligands epidermal growth factor ( EGF ) , transforming growth factor alpha ( TGF alpha ) , amphiregulin ( AR ) , cripto , and the receptors , epidermal growth factor receptor ( EGF R ) , and c erbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
C erbB 2 oncoprotein and the epidermal growth factor receptor ( EGFR ) protein are transmembrane glycoproteins with an external ligand binding domain and a nearly homologous internal tyrosine kinase domain . ^^^ The correlative analysis resulted in a significant positive homology with increasing grading level between the expression of EGFR and c erbB 2 protein . ^^^ The results emphasize that EGFR and c erbB 2 protein were expressed in astrocytic tumors with increased malignancy and dedifferentiation . . ^^^ Coexpression of epidermal growth factor receptor protein and c erbB 2 oncoprotein in human astrocytic tumors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
OBJECTIVE : To investigate c jun oncoprotein expression in transitional cell carcinomas ( TCCs ) of the urinary bladder and to determine its relationship to tumour grade and stage , and to the expression of epidermal growth factor receptor ( EGFR ) , c erbB 2 and p 53 oncoproteins . ^^^ MATERIALS AND METHODS : The expression of c jun was studied using immunohistochemistry in a series of 48 TCCs of known EGFR , c erbB 2 and p 53 status . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
First , data from in vitro experiments indicate that overexpression of either EGFR or p185c neu ( or the human homolog c erbB 2 ) transforms cell lines . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Correlation of c erbB 2 protein ( n = 44 ) , epidermal growth factor receptor ( EGFR ) ( n = 41 ) expression , and DNA ploidy pattern ( n = 42 ) with clinical outcomes of human colorectal cancers was studied . ^^^ Using monoclonal antibodies against c erbB 2 protein and EGFR , an immunohistochemical study of the expression of c erbB 2 protein and EGFR in frozen tissue sections from the lesion was performed . ^^^ The results above suggest that the expression of c erbB 2 protein or EGFR was associated with distant metastasis , while on the other hand DNA ploidy pattern was correlated with lymph node metastasis . . ^^^ Study of c erbB 2 protein and epidermal growth factor receptor expression and DNA ploidy pattern in colorectal carcinoma . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
An immunohistochemical study of the expression of epidermal growth factor receptor ( EGFR ) and c erbB 2 protein was performed in fresh frozen sections from 30 patients with transitional cell cancers ( TCCs ) of the upper urinary tract ( 15 renal pelvic cancers , 15 ureteral cancers ) who underwent total nephroureterectomy . ^^^ Thirteen of those 30 TCCs ( 43 . 3 % ) showed increased expression of EGFR , and 11 TCCs ( 36 . 7 % ) showed increased expression of c erbB 2 . ^^^ On the other hand , in 11 of 20 ( 55 . 0 % ) patients whose tumours had increased EGFR and / or c erbB 2 expression , secondary urinary bladder cancers recurred after surgery ( P < 0 . 05 ) . ^^^ Thus , the recurrence rate of TCCs with increased EGFR and / or c erbB 2 expression was significantly higher than that of tumours showing no increased expression of these receptors ( P < 0 . 01 ) . ^^^ These results suggest that the immunohistochemical detection of the expression of EGFR and c erbB 2 in urothelial cancers of the upper urinary tract might be a useful method for determining the likelihood of secondary bladder cancer recurrences . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Formalin fixed , paraffin embedded tissue sections from twenty radical prostatectomy specimens were immunostained with validated rabbit polyclonal antibodies raised against human EGFR and c erbB 2 , using the streptavidin peroxidase enzyme conjugate method . ^^^ Moreover , EGFR and c erbB 2 appeared to be colocalized as well as independently expressed by different subpopulations of NE cells . ^^^ Overexpression of human epidermal growth factor receptor and c erbB 2 by neuroendocrine cells in normal prostatic tissue . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunohistochemical study of the coexpression of epidermal growth factor receptor ( EGFR ) and c erbB 2 protein in colorectal cancer ] . ^^^ The coexpression of EGFR and c erbB 2 protein was examined immunohistochemically in a total of 62 freshly frozen specimens of colorectal cancer , and correlations between the coexpression of both receptors and their clinicopathological variables were analyzed . ^^^ These results suggest that the coexpression of EGFR and c erbB 2 protein may be related to the distant metastasis of colorectal cancer . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The epidermal growth factor receptor ( EGF R , c erbB 1 ) , Her 2 / neu ( c erbB 2 ) , and c erbB 3 are members of the erbB family . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Two structurally related tyrosine kinase growth factors , the epidermal growth factor receptor ( EGFR ) and c erbB 2 ( neu ) have been identified in human breast cancer tissue and , in many instances , may function as oncogenes . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The c erbB 2 gene encodes a M ( r ) 185 , 000 tyrosine kinase receptor ( p 185 ) with extensive homology to the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Expression of metastasis related nm 23 H1 and nm 23 H2 genes in ovarian carcinomas : correlation with clinicopathology , EGFR , c erbB 2 , and c erbB 3 genes , and sex steroid receptor expression . ^^^ To verity the role of metastasis related nm 23 genes in carcinogenesis and progression of ovarian carcinoma , we analyzed the mRNA levels of the nm 23 genes of both isoforms , H 1 and H 2 , together with those of the epidermal growth factor receptor , the c erbB 2 , and the c erbB 3 genes in 45 ovarian carcinomas and 5 benign cystadenomas . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Moreover , the epidermal growth factor receptor and the c erbB 2 oncogene seem to be implicated in the pathogenesis and behaviour of several cancers , including breast cancer . c erbB 3 is a new member of the type 1 receptor family for which there is currently little information available on its expression in neoplastic tissues , and on its possible prognostic significance . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The authors studied the role of 70 Kd heat shock protein ( HSP 70 ) in the progression of breast cancer by examining the correlation between the expression of HSP 70 and epidermal growth factor receptor , c erbB 2 , p 53 , and estrogen receptor in 124 cases of invasive primary human breast cancers . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
This study was undertaken to define the prognostic value of the overexpression of p 53 protein , c erbB 2 protein , EGFr protein and PCNA in gastric carcinomas . ^^^ Overall , 34 % of gastric carcinomas had nuclear staining for p 53 protein , 34 % of carcinomas membrane staining for the c erbB 2 and 74 % of carcinomas membrane and cytoplasmic staining for EGFr , showing distribution in a heterogeneous fashion . ^^^ Immunohistochemical detection of p 53 protein , c erbB 2 protein , epidermal growth factor receptor protein and proliferating cell nuclear antigen in gastric carcinoma . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The expressions of p 53 and EGFR were interrelated , while expression of c erbB 2 was independent of EGFR expression . ^^^ Expression of epidermal growth factor receptor in bladder cancer as related to established prognostic factors , oncoprotein ( c erbB 2 , p 53 ) expression and long term prognosis . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
However , the prognostic value of positive EGFr EIA status was weaker than that of c erbB 2 overexpression . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Epidermal growth factor receptor expression in breast cancer : association with response to endocrine therapy . 106 previously untreated breast cancer patients have been immunohistochemically analysed for EGF R , ER , Ki 67 , and c erbB 2 product . ^^^ No association was observed between EGF R and the c erbB 2 product . ^^^ The presence of c erbB 2 protein product did not influence endocrine sensitivity in any of the ER / EGF R sub groups . . ^^^ Epidermal growth factor receptor expression in breast cancer : association with response to endocrine therapy . 106 previously untreated breast cancer patients have been immunohistochemically analysed for EGF R , ER , Ki 67 , and c erbB 2 product . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The type 1 family of growth factor receptors includes the EGFR , c erbB 2 , c erbB 3 , and c erbB 4 . ^^^ The EGFR gene and more frequently the c erbB 2 gene are amplified in a proportion of cases . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
No significant correlation was found between EGFR status and tumor size , nodal metastases , or the expression of c erbB 2 protein . ^^^ The group expressing EGFR and c erbB 2 protein indicated a particularly high risk for relapse . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We investigated the relation of c erbB 2 and int 2 gene amplification , expression , ER and EGFR with clinical characteristics . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunohistochemical detection of TGF alpha , EGF R , c erbB 2 , c H ras , c myc , estrogen and progesterone in benign and malignant human breast lesions : a concomitant expression . ^^^ The expression of transforming growth factor alpha ( TGF alpha ) , epidermal growth factor receptor ( EGF R ) and oncogenes c erbB 2 , c H ras , c myc , as well as estrogen ( ER ) and progesterone ( PR ) receptors were studied immunohistochemically in the tissue of 21 benign and 58 malignant human breast lesions . ^^^ Twenty nine ( 50 % ) of 58 carcinomas were positive for EGF R and c erbB 2 product , 55 ( 94 . 8 % ) for c myc product , 9 ( 15 . 5 % ) for c H ras product and 17 ( 29 % ) for TGF alpha . ^^^ However , a significant positive correlation was observed between lymph node involvement and c erbB 2 and EGF R / c erbB 2 positive tumors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
OBJECTIVE : To determine whether the presence or absence of the oncoproteins epidermal growth factor receptor ( EGFR ) and c erbB 2 could predict tumour behaviour . ^^^ PATIENTS AND METHODS : Tissue from 45 stage A 1 ( T1a ) prostatic adenocarcinomas from patients with a mean age of 65 years were immunostained for EGFR ( 12E ) and c erbB 2 ( NCL CB 11 ) . ^^^ RESULTS : Forty percent ( 18 of 45 ) and 36 % ( 16 of 45 ) of patients respectively were EGFR and c erbB 2 positive in the tumour . ^^^ Expression of these tyrosine kinase oncogenes was not confined to the tumour and the surrounding hyperplastic prostate was also positive for EGFR in 76 % ( 34 / 45 ) of patients and for c erbB 2 in 16 % ( 11 of 45 ) . ^^^ EGFR and c erbB 2 expression was weakly associated in both benign and malignant epithelium . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Abnormal expression of p 53 , transforming growth factor alpha ( TGF alpha ) , epidermal growth factor receptor ( EGFR ) , and c erbB 2 occurs in a variety of cancers and in some cases is associated with poor prognosis . ^^^ Expression of p 53 , transforming growth factor alpha , epidermal growth factor receptor , and c erbB 2 in endometrial carcinoma and correlation with survival and known predictors of survival . ^^^ Epidermal growth factor receptor staining did not correlate with length of survival or known prognostic variables . c erbB 2 staining correlated with tumor type . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The expression of epidermal growth factor receptor ( EGF R ) , c erbB 2 proto oncogene , and estrogen receptor ( ER ) was studied immunohistochemically in a series of 97 human papillomavirus ( HPV ) lesions of the uterine cervix , with special emphasis on their association with the HPV type , grade of intraepithelial neoplasia ( CIN ) , and the natural history of the disease . ^^^ No clear cut associations were established between the EGF R , c erbB 2 , or ER expression and HPV type , nor in CIN or the clinical course of HPV infections . ^^^ This failure for EGF R , c erbB 2 , and ER to be associated with the specific HPV types , grade of CIN , or the clinical course of cervical HPV lesions suggests that the assessment of these factors is of limited value in explaining the development of HPV associated CIN and in predicting the prognosis of this disease . . ^^^ Epidermal growth factor receptor , c erbB 2 proto oncogene and estrogen receptor expression in human papillomavirus lesions of the uterine cervix . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
All other growth factors and their receptors examined ( TGF alpha , EGFR , c met and c erbB 2 ) remained constant and were not affected by HGF treatment . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunocytochemical analyses of EGF , EGFR , and c erbB 2 ( an EGFR related oncoprotein ) were carried out on paraffin embedded sections of 54 pituitary tumors . ^^^ The expression of c erbB 2 was detected in all normal tissue , all NFT , and about half of GH secreting tumors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The expression of c jun oncogene has been examined in normal , benign , and malignant breast tissues , and c jun specific immunoreactivity in carcinomas has been related to histological type , tumour grade , c erbB 2 , oestrogen receptor , progesterone receptor , and epidermal growth factor receptor expression . ^^^ There was no significant relationship between c jun oncoprotein expression and c erbB 2 , oestrogen , progesterone , and epidermal growth factor receptor immunoreactivity . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Expression of EGF , TGF alpha , EGFR and c erbB 2 genes and their gene products in human pancreatic carcinoma cell lines . ^^^ The expression of mRNA for epidermal growth factor ( EGF ) , transforming growth factor alpha ( TGF alpha ) , EGF receptor ( EGFR ) and c erbB 2 genes and the immunoreactivity to these gene products were examined in 3 newly established human pancreatic carcinoma cell lines and their corresponding in vivo tumor lines using the Northern blot technique and the immunohistochemical method . ^^^ All 3 cell lines expressed TGF alpha , EGFR and 2 of the 3 lines expressed EGF and c erbB 2 mRNAs . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Reciprocal expression of epidermal growth factor receptor ( EGF R ) and c erbB 2 by non invasive and invasive human trophoblast populations . ^^^ The epidermal growth factor receptor ( EGF R ) and c erbB 2 proto oncogene products are two closely related tyrosine kinase receptors which are expressed in high amounts in human placenta . ^^^ In this study , we have investigated the expression of EGF R and c erbB 2 proteins by different trophoblast populations using immunohistochemistry . ^^^ This precise spatial expression suggests that EGF R plays an important role in trophoblast proliferation whereas c erbB 2 may be important for trophoblast invasion and differentiation . ^^^ Isolated trophoblasts were shown not to overexpress c erbB 2 , and no differences in either EGF R or c erbB 2 expression were seen between normal and malignant trophoblasts . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The epidermal growth factor receptor ( EGFR ) is structurally similar to the c erbB 2 oncogene protein . ^^^ One hundred and nineteen specimens of primary human lung adenocarcinoma were investigated immunohistochemically for the expression of EGFR and the c erbB 2 protein . ^^^ Positive staining for EGFR was evident in 55 ( 46 % ) , and c erbB 2 protein in 33 ( 28 % ) cases . ^^^ Of the 119 cases , the number staining positively for both the EGFR and c erbB 2 protein totalled 16 ( 13 % ) . ^^^ The incidence of both the expression of EGFR and the c erbB 2 protein was greater in patients with metastasis 1 ( M 1 ) than in those with M 0 ( P < 0 . 01 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
DNA ploidy , S phase fraction , mitotic index , morphometric nuclear features , and expression of c erbB 2 , p 53 , and epidermal growth factor receptor were independent of expression of pS 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The c erbB 2 proto oncogene encodes a receptor tyrosine kinase ( RTK ) closely related to the epidermal growth factor receptor ( EGFR ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The protein was inversely related to 2 markers of endocrine insensitivity , epidermal growth factor receptor ( EGFR ) and c erbB 2 oncoprotein , while no associations were observed with either transforming growth factor ( TGF ) alpha or Ki 67 proliferative status . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
For immunostaining , antibodies reacting with epithelial membrane antigen ( EMA ) , pankeratin , vimentin , CA 125 , CA 19 9 , carcinoembryonic antigen ( CEA ) , alpha fetoprotein ( AFP ) , alpha 1 antitrypsin ( AT ) , epidermal growth factor receptor ( EGFR ) , c erbB 2 , bcl 2 and p 53 proteins were used . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
METHODS The expression of the insulin like growth factor 1 receptor ( ILGFR 1 ) , epidermal growth factor receptor ( EGFR ) , and the c erbB 2 , c ras , and c myc products was studied by multiparameter flow cytometry in 80 patients with epithelial ovarian cancer for whom long term follow up was available . ^^^ RESULTS Overexpression of ILGFR 1 , EGFR , c erbB 2 , c ras and c myc was found in , respectively , nine of 80 ( 11 % ) , 10 of 80 ( 12 % ) , 19 of 80 ( 24 % ) , 16 of 80 ( 20 % ) and 28 of 80 ( 35 % ) ovarian carcinomas . ^^^ The levels of expression of ILGFR 1 , EGFR , c erbB 2 and c ras were significantly higher in the tumours of patients with recurrent or persistent disease after chemotherapy than in the tumours of patients at initial presentation ( p < 0 . 02 ) . ^^^ Expression of c erbB 2 , c myc , and c ras oncoproteins , insulin like growth factor receptor 1 , and epidermal growth factor receptor in ovarian carcinoma . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The significance of EGFR as an oncogene in breast cancer is compounded by its potential interactions with other oncogenes such as c erbB 2 and c myc . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Differentiation and proliferation patterns in human trophoblast revealed by c erbB 2 oncogene product and EGF R . ^^^ We have studied the expression of epidermal growth factor receptor ( EGF R ) and the receptor encoded by the c erbB 2 proto oncogene in first and third trimester human placentas . ^^^ Concerning the extravillous trophoblast in cell islands and cell columns , EGF R was expressed in the cells proximal to the villous stroma whereas the distal cells were c erbB 2 positive . ^^^ Our data indicate that EGF R expression is strongly related to the proliferative trophoblast and , with advancing pregnancy , to the differentiated villous trophoblast . off contrast , expression of c erB 2 protein product occurs only in more advanced stages of trophoblast differentiation , although transcripts of c erbB 2 are found in both proliferative and differentiated trophoblast . ^^^ In addition , the coexpression of EGF R and c erbB 2 protein product in the syncytiotrophoblast suggests their involvement in complex regulation of hormones and growth factors . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
All of the mAbs immunoprecipitated the 170 kDa glycoprotein from cells expressing the EGFR but not the 185 kDa product of the related c erbB 2 proto oncogene . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The human c erbB 2 protooncogene product ( erbB 2 protein ) is a 185 kilodalton glycoprotein closely related to epidermal growth factor receptor protein . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The mRNA expression of transforming growth factor alpha ( TGF alpha ) , epidermal growth factor receptor ( EGFR ) , c erbB 2 and c met proto oncogenes in eight newly established cell lines and 29 primary tumors of human non small cell lung carcinoma ( NSCLC ) have been investigated . ^^^ In vitro , the expressions of TGF alpha , c erbB 2 , and c met were consistently high in adenocarcinomas , while EGFR was expressed highest in a squamous cell carcinoma cell line . ^^^ There was linear correlation between the levels of expression of TGF alpha and EGFR or c erbB 2 , and between EGFR and c erbB 2 . ^^^ The c met expression was also correlated with those of TGF alpha , EGFR , and c erbB 2 . ^^^ In vivo , The mean mRNA levels of TGF alpha , EGFR , and c met , but not c erbB 2 , were higher in carcinomas than in normal lung tissues ( 2 . 8 , 1 . 7 , and 3 . 0 times , respectively ) ; however , only adenocarcinomas expressed a significantly higher level of c erbB 2 than their corresponding normal tissues ( 2 . 2 times ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We analyzed by immunohistochemistry 19 typical lung carcinoids for the expression of the epidermal growth factor ( EGF ) , transforming growth factor alpha ( TGF alpha ) , EGF receptor ( EGFr ) , and EGFr related c erbB 2 protein ( p 185 ) . ^^^ Thus , EGFr was coexpressed with its ligands , TGF alpha and EGF , and the receptor encoded by c erbB 2 was detected in carcinoids positive for EGFr and TGF alpha . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
This investigation has evaluated the gene amplification and expression of EGF R and the homologous oncogene c erbB 2 in soft tissue and osseous sarcomas by Southern and northern blot analysis . ^^^ Amplification of EGF R and c erbB 2 was identified in 2 of 117 ( 1 . 7 % ) and 6 of 105 ( 5 . 7 % ) of the sarcomas , respectively . ^^^ Increased expression of EGF R and c erbB 2 was identified in 21 of 43 ( 49 % ) and 35 of 94 ( 37 % ) sarcomas , respectively . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Relationship between EGF R , c erbB 2 protein expression and Ki 67 immunostaining in breast cancer and hormone sensitivity . ^^^ The expression of the epidermal growth factor receptor ( EGF R ) , c erbB 2 protein product and Ki 67 have been evaluated in 105 breast cancers of known responsiveness to endocrine therapy using immunohistochemistry . ^^^ Subdivision of the EGF R data according to c erbB 2 measurements revealed an association between c erbB 2 immunostaining and worsened patient outlook and hormone insensitivity in moderately EGF R positive tumours . c erbB 2 immunostaining in highly EGF R positive tumours did not further contribute to the already poor prognosis of these patients . ^^^ These data confirm the prognostic importance of EGF R measurements in breast cancer and may infer a functional interaction between this protein and the c erbB 2 protein product in the aberrant growth of a subset of breast tumours . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We examined 190 fresh , frozen thyroid tissue samples from 70 patients by immunohistochemistry with antibodies to EGF r , TGF alpha , c erbB 2 and c myc . ^^^ EGF r expression was detected in 17 out of 19 papillary carcinomas , TGF alpha expression in 10 , and c erbB 2 expression in 15 . ^^^ Concomitant expression of EGF r , TGF alpha and c erbB 2 was seen in 7 papillary carcinomas . ^^^ No EGF r , TGF alpha or c erbB 2 immunopositivity was found in normal appearing thyroid tissue ( 25 cases ) , whereas a few of the non neoplastic lesions ( colloid goitres and diffuse hyperplasias ) expressed either EGF r or TGF alpha . c myc expression was detectable in all tissue samples , and expression was invariably nuclear . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
However , a small number of positive cells for EGFR ( 8 . 5 % ) , c erbB 2 ( 11 . 3 % ) , p 53 ( 11 . 3 % ) and c K ras ( 1 . 7 % ) were found in ATP . ^^^ The percentages of positive cells for EGFR ( 1 . 5 % ) and c erbB 2 ( 4 . 5 % ) were very low in intestinal metaplasia . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunohistochemical staining for EGF , EGFR , c erbB 2 , p 53 , K ras and PCNA was performed on the formalin fixed , paraffin embedded sections of resected gastric carcinomas . ^^^ A relatively high positive rate was observed for EGFR and c erbB 2 in the well differentiated adenocarcinomas and p 53 in the poorly differentiated adenocarcinomas . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Inhibition of human lung cancer cell line growth by an anti p185HER2 antibody . p185HER2 , the product of the c erbB 2 or HER 2 gene , is a membrane bound tyrosine kinase that has structural similarity to the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The c erbB 2 ( HER 2 / neu ) protein is a membrane glycoprotein growth factor receptor showing molecular homology with the epidermal growth factor receptor ( EGFR ) . ^^^ In endometrial carcinomas , little is known about the relationship between the expression of c erbB 2 protein and that of EGFR . ^^^ Of the 34 patients , 22 ( 64 . 7 % ) had c erbB 2 protein positive and EGFR negative tumor , and 8 ( 23 . 5 % ) had tumor positivity for both proteins . ^^^ However , expression of EGFR in addition to c erbB 2 protein was more frequently observed with advancing stage of disease and was inversely correlated with the grade of differentiation and with the expression of ER or PR of the tumor . ^^^ The expression of EGFR , in addition to that of c erbB 2 protein , is an important event that presumably is linked with progression or with a poorly differentiated state of endometrial carcinomas . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
No relationship exists between EGF R expression , c erbB 2 ( 3B5 clone , Oncogene Science ) expression , tumor size and lymph node status . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
CONCLUSIONS The very low incidence of EGF R positive cases in the `` special type ' ' group of breast carcinomas with a good prognosis is in line with the absence of the homologous c erbB 2 and p 53 oncoproteins , and the rarity of highly proliferating and oestrogen / progesterone negative cases . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Forty six primary vaginal carcinomas were examined immunohistochemically for expression of retinoblastoma ( RB ) protein , epidermal growth factor receptor ( EGFR ) , and c erbB 2 oncoprotein . ^^^ Fifteen and 11 % of the cases showed increased expression of EGFR and c erbB 2 oncoprotein , respectively , indicating that these oncoproteins may be involved in the neoplastic process of a minority of vaginal carcinomas . ^^^ Overexpression of EGFR and c erbB 2 oncoprotein had no prognostic significance in vaginal carcinomas . . ^^^ Expression of retinoblastoma tumor suppressor gene protein , epidermal growth factor receptor , and c erbB 2 oncoprotein in primary vaginal carcinomas . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Neither c erbB 2 , EGF R , p 53 nor any of the other factors showed any correlation to survival . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PTB domain mediated interaction with the NXX ( pY ) motif of c ErbB 2 was characterized by similar overall affinity but slower kinetics than that reported for SH 2 domains . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We observed no correlation between abnormalities of the p 53 and the Rb gene products or between elevated c erbB 2 or epidermal growth factor receptor ( EGFR ) expression and immunodetection of p53 . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
EGF R and overexpression of the oncogene c erbB 2 in ovarian cancer : immunohistochemical findings and prognostic value . ^^^ PURPOSE : The purpose of this study was to investigate the prognostic value of EGF R ( c erbB 1 ) compared to the overexpression of the c erbB 2 oncogene product p 185 in ovarian cancer . ^^^ EGF R and c erbB 2 oncogene product p 185 have been evaluated using immunohistochemistry . ^^^ RESULTS : EGF R was detected in 13 % , and c erbB 2 oncogene product p 185 in 18 % of primary tumors . ^^^ EGF R showed no significant impact on the survival time , whereas c erbB 2 oncogene product p 185 positive patients had a significantly worse prognosis compared to p 185 negative cases ( p = 0 . 002 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
There is differential expression of the epidermal growth factor receptor ( EGF R ) and c erbB 2 proteins on villous and extravillous trophoblast populations . ^^^ Using monoclonal antibodies to EGF R and c erbB 2 , we have obtained highly purified populations of villous and extravillous trophoblast by fluorescence activated cell sorting . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The amplification of the c erbB 2 oncogene was investigated in protein overexpression cases by dual colour fluorescence in situ hybridisation ( FISH ) . p 185 overexpression was correlated with p 53 and epidermal growth factor receptor ( EGFR ) expression , as well as with clinicopathological features . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
This study was conducted to determine the prognostic significance of tumor angiogenesis , c erbB 2 , epidermal growth factor receptor , Ki 67 , and p 53 for patients with nasopharyngeal carcinoma . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In the present study , the authors examined the expression of the epidermal growth factor receptor homologue , HER 2 / neu ( c erbB 2 ) , in pancreatic duct lesions adjacent to infiltrating pancreas cancers in a series of 19 cases of pancreatic duct adenocarcinoma . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Epidermal growth factor receptor ( EGFR ) and c erbB 2 ( also known as HER 2 / neu ) oncoprotein ( p185erbB 2 ) are members of the subfamily of tyrosine kinase , transmembrane receptors often implicated in human carcinogenesis . ^^^ Epidermal growth factor receptor and c erbB 2 oncoprotein expression in female genital tract carcinosarcomas ( malignant mixed mllerian tumors ) . ^^^ Epidermal growth factor receptor ( EGFR ) and c erbB 2 ( also known as HER 2 / neu ) oncoprotein ( p185erbB 2 ) are members of the subfamily of tyrosine kinase , transmembrane receptors often implicated in human carcinogenesis . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Oncoproteins and tumor progression in papillary thyroid carcinoma : presence of epidermal growth factor receptor , c erbB 2 protein , estrogen receptor related protein , p 21 ras protein , and proliferation indicators in relation to tumor recurrences and patient survival . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Coexisting overexpression of epidermal growth factor receptor , c erbB 2 , c erbB 3 , and c erbB 4 was demonstrated in 36 ( 64 % ) of 56 papillary thyroid carcinomas . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The tyrosine kinase receptor family , including the epidermal growth factor receptor ( EGF R ) , c erbB 2 and , more recently , the c erbB 3 , has been recognized as being of particular importance in many human malignancies . ^^^ EGF R was not detected in any of these samples but c erbB 2 and c erbB 3 gene products ( ERBB2and ERBB 3 ) were demonstrated in all A . ^^^ EGF R was not detected in any of these samples but c erbB 2 and c erbB 3 gene products ( ERBB2and ERBB 3 ) were demonstrated in all A . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Formalin fixed , paraffinembedded specimens were immunostained for epidermal growth factor ( EGF ) , transforming growth factor alpha ( TGFalpha ) , cripto , EGF receptor ( EGFR ) and c ERBB 2 gene product . ^^^ Of the 68 early colorectal carcinomas , EGF , TGF alpha , cripto , EGFR and c ERBB 2 products were detected at various degrees 24 ( 35 % ) , 50 ( 74 % ) , 31 ( 46 % ) , 11 ( 16 % ) , and 34 ( 50 % ) , respectively . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The expression of epidermal growth factor receptor ( EGFR ) , c erbB 2 , and c erbB 3 was examined immunohistochemically in 57 cases of periampullary carcinoma . ^^^ In carcinoma of the head of pancreas , the percentage of cases with overexpression of c erbB 3 was significantly higher than with overexpression of c erbB 2 and EGFR . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Northern blot analysis also revealed that CD26 / DPP 4 is a more specific marker of differentiated carcinoma than three proto oncogenes previously reported to increase mRNA expression in thyroid carcinomas : c met , c erbB 2 , and EGF R . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
BACKGROUND : This study evaluated the prognostic significance of immunohistochemical staining for cathepsin D , epidermal growth factor receptor ( EGFR ) , and c erbB 2 in patients with early cervical squamous cell carcinoma . ^^^ Evaluation of the prognostic significance of cathepsin D , epidermal growth factor receptor , and c erbB 2 in early cervical squamous cell carcinoma . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Epidermal growth factor receptor ( EGFR ) expression by human breast cancer has been shown to predict poor patient outcome , as has amplification of the c erbB 2 proto oncogene . ^^^ Quantitative estimation of epidermal growth factor receptor and c erbB 2 in human breast cancer . ^^^ Epidermal growth factor receptor ( EGFR ) expression by human breast cancer has been shown to predict poor patient outcome , as has amplification of the c erbB 2 proto oncogene . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Furthermore , the trophoblast IFNs inhibited the expression of proto oncogenes such as EGF R , c erbB 2 and c fms reported to be involved in normal trophoblast growth and differentiation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The expression of c erbB 2 oncoprotein , epidermal growth factor receptor ( EGFR ) and estrogen receptor ( ER ) was evaluated by the immunoperoxidase technique ( PAP ) in ductal breast carcinomas . ^^^ Stratifying of patients on the basis of c erbB 2 , EGFR and ER status indicated that the combination of c erbB 2 overexpression accompanied by high EGFR value and undetectable ER , identified poorly differentiated tumors and patients with high incidence of axillary lymph node metastases , while high EGFR expression and negative c erbB 2 staining was connected only with poor tumor grade . ^^^ Our results indicate that the comparison of c erbB 2 , EGFR and ER status seems to be a powerful tool in discriminating breast carcinomas with different biological phenotypes . . ^^^ Relationship between c erbB 2 oncoprotein , epidermal growth factor receptor , and estrogen receptor expression in patients with ductal breast carcinoma . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The growth fraction ( MIB 1 ) , oestrogen receptor ( ER ) , progesterone receptor ( PR ) , p 53 mutant protein , c erbB 2 , epidermal growth factor receptor ( EGFR ) , NCRC11 / epithelial membrane antigen ( EMA ) and DNA plopidy were examined . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The class 1 growth factor receptor family includes epidermal growth factor receptor , i . e . c erbB 1 , c erbB 2 and c erbB 3 molecules . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The c erbB 2 proto oncogene ( HER 2 / neu ) codes for a transmembrane , tyrosine kinase , 185 kD oncoprotein ( p185erbB2 ) , which is related to the epidermal growth factor receptor . p185erbB2 overexpression occurs in carcinomas at many sites , including the uterine cervix , and predicts poor clinical outcome . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Prognostic significance of epidermal growth factor receptor ( EGFR ) and c erbB 2 protein overexpression in adenocarcinoma of the uterine cervix . ^^^ The authors studied the prognostic value of EGFR and c erbB 2 overexpression in adenocarcinoma of the uterine cervix . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
EGF receptor ( EGF R ) and c erbB 2 are homologous tyrosine kinase transmembrane receptors . ^^^ We studied the location of EGF R and c erbB 2 in 100 samples of normal breast with standard immunohistochemical methods and double labelling techniques . ^^^ EGF R was mainly expressed on the stroma and myoepithelial cells , whereas c erbB 2 expression was exclusively epithelial . ^^^ EGF R and c erbB 2 expression on epithelial cells was stronger during the luteal phase than the follicular phase ( p < 0 . 01 for EGF R ) . ^^^ Epidermal growth factor receptor and c erbB 2 expression in normal breast tissue during the menstrual cycle . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Two new immunoenzymatic assays for c erbB 2 oncoprotein and epidermal growth factor receptor ( EGF R ) ( Oncogene Science ) in human breast cancer were validated . ^^^ The accuracy of c erbB 2 oncoprotein and EGF R assays was examined by using dilution and recovery tests throughout the standard curves . ^^^ Furthermore , a significant positive correlation was observed between EGF R levels and c erbB 2 oncoprotein levels . ^^^ In conclusion , immunoenzymatic assays of EGF R and c erbB 2 oncoprotein are easy to use , sensitive and reliable . ^^^ The accurate standardisation of immunoenzymatic assays could contribute to the clinical use of EGF R and c erbB 2 oncoprotein as prognostic factors in breast cancer . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The pattern and extent of reactivity has been correlated with clinicopathological data including tumour type , grade and lymph node status and with other prognostic parameters including oestrogen receptor ( ER ) status , expression of c erbB 2 , pS 2 protein and epidermal growth factor receptor ( EGFR ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The prognostic significance of epidermal growth factor receptor ( EGFR ) , C erbB 2 , Ki 67 and PCNA expression in breast cancer . ^^^ The evaluation of the immunohistochemical expression of epidermal growth factor receptor ( EGFR ) , c erbB 2 oncoprotein , proliferating indices Ki 67 , and PCNA were determined on 68 primary breast carcinomas . ^^^ There was almost equally high staining intensity at the membranus for EGFR and c erbB 2 in about 32 % of the cases . ^^^ The EGFR and c erbB 2 positive cases were much less common in infiltrating lobular ( 2 , 2 / 13 ) rather than in ductal adenocarcinomas ( 21 , 20 / 55 ) . ^^^ The low grade carcinomas showed low expression of EGFR and c erbB 2 oncoprotehl comparing with high grade ductal adenocarcinomas . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Epidermal growth factor receptor gene and c erbB 2 gene amplification in ovarian cyst fluid . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
No significant correlations were observed between apparent loss of pRB and tumour size , parity , patient lymph node status , p 53 , c erbB 2 , c jun , EGFR or steroid hormone receptor expression . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Neither some histochemical reactions nor the well preserved immunohistochemical reactivities of beta hCG , hPL , PLAP , AFP , cytokeratin , vimentin , desmin , factor 8 , CD 68 , MIB 1 ( growth fraction ) , EGF R , p 53 and c erbB 2 oncoproteins have disclosed specific chromosome anomalies . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
On examining the breast tumours , alpha JSB 1 showed a positive association with c erbB 2 ( P = 0 . 003 ) , c myc ( P = 0 . 0004 ) and c jun ( P = 0 . 02 ) but not ER or EGF R expression . alpha GSTpi showed a positive association with c erbB 2 ( P = 0 . 03 ) and c myc ( P = 0 . 0004 ) but not ER , EGF R or c jun . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Recently , EGFR and c erbB 2 protein was found to regulate cell adhesion and the invasive growth of cancer through its association with the cadherin catenin complex . ^^^ In this study we investigate the combined role of tumoral neoangiogenesis and c erbB 2 / EGFR expression in the metastatic behaviour and prognosis of operable non small cell lung cancer . 107 tumour samples from patients suffering from operable non small cell lung cancer were examined . ^^^ EGFR and c erbB 2 were not correlated with each other . ^^^ The absence of expression of both c erbB 2 and EGFR oncogenes in tumours with high angiogenesis , was most frequently observed in node negative cases ( p = 0 . 04 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The overexpression of c erbB 2 protein ( ErbB 2 ) , epidermal growth factor receptor ( EGFR ) , and / or cathepsin D ( CD ) in breast cancer is known to be a poor prognostic factor . ^^^ Simultaneous quantitative analyses of c erbB 2 protein , epidermal growth factor receptor , cathepsin D , and hormone receptors in breast cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Epidermal growth factor receptor ( EGF R ) expression was seen in 86 % of cases and had no prognostic significance . c erbB 2 was expressed in 50 % of cases and was inversely related to a poor prognosis . ^^^ Evaluation of epidermal growth factor receptor , transforming growth factor alpha , epidermal growth factor and c erbB 2 in the progression of invasive bladder cancer . ^^^ Epidermal growth factor receptor ( EGF R ) expression was seen in 86 % of cases and had no prognostic significance . c erbB 2 was expressed in 50 % of cases and was inversely related to a poor prognosis . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Effects of human trophoblast induced interferons on the expression of proto oncogenes c fms / CSF 1R , EGF R and c erbB 2 in invasive and non invasive trophoblast . ^^^ The invasive trophoblast cells expressed colony stimulating factor receptor ( c fms / CSF 1R ) and c erbB 2 proteins but low levels of EGF R . ^^^ We studied the effects of human trophoblast induced interferon ( IFN ) alpha / beta on the expression of c fms / CSF 1R , EGF R and c erbB 2 whose ligands are reported to be involved in the regulation of growth and differentiation of normal invasive and non invasive trophoblast cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The aim of this study , therefore , is to determine the prognostic relevance of growth factor receptor expression [ c erbB 2 , epidermal growth factor receptor ( EGFR ) and transforming growth factor beta receptor ( TGF beta R ) ] in such patients . ^^^ The expression of EGFR and TGF beta R and the protein production of c erbB 2 were detected using standard immunohistochemical techniques . ^^^ The expression of EGFR and TGF beta R and the presence of the c erbB 2 protein product were not identified as independent prognostic factors for survival . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The recent highlighted points in prognostic factors after breast cancer operation include : 1 ) the emergence of many genetic and biochemical markers , including c erbB 2 , int 2 , EGFR , p 53 , nm 23 , LOH , E cadherin , s phase fraction . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
High c erbB 3 protein expression is associated with shorter survival in advanced non small cell lung carcinomas . c erbB 3 is a new member of the Type 1 growth factor receptor family that includes epidermal growth factor receptor ( also called c erbB 1 ) and HER 2 / neu ( also called c erbB 2 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Multivariate analysis of DNA ploidy , p 53 , c erbB 2 proteins , EGFR , and steroid hormone receptors for prediction of poor short term prognosis in breast cancer . ^^^ BACKGROUND : Several molecular genetic alterations in breast cancer , including aneuploidy , aberrant expression of p 53 , c erbB 2 and EGFR , have been associated with poor prognosis in breast cancer patients particularly those who are lymph node negative . ^^^ On the same specimens steroid hormone receptors ( ER and PR ) were measured in the cytosol fraction using Abbott ELIZA assays , c erbB 2 and EGFR were determined in the membrane fraction and mutant p 53 protein in the nuclear fraction by Oncogene Science ELISA procedures . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The c erbB 2 protein , a member of EGFR family was also expressed in HSG cells and was involved in the growth signal pathway of HSG cells as well as EGFR . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
An immunohistochemical analysis of overexpression of epidermal growth factor receptor ( EGFR ) , c erbB 2 , and p 53 proteins was performed on 43 biopsies of laryngeal epithelial hyperplastic lesions ( EHLL ) , classified according to the Kambic Lenart classification , and in 11 cases of laryngeal carcinoma ( SCCL ) . ^^^ Epidermal growth factor receptor , c erbB 2 and p 53 overexpressions in epithelial hyperplastic lesions of the larynx . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The class 1 tyrosine kinase growth factor receptors include epidermal growth factor receptor ( EGFR ) , ErbB 2 ( c erbB 2 , HER 2 / neu ) , ErbB 3 and ErbB 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
An investigation of the effects of phenotypic expression of estrogen receptors ( ER ) , the progesterone receptors , c erbB 2 oncoprotein and epidermal growth factor receptors ( EGFR ) on the capacity of HMEC cells to grow in vitro as monolayers showed that expression of ER and EGFR is required for controlling tumor proliferative activity in vitro . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
While numerous studies on the immunohistochemical demonstration of EGFR overexpression have been reported , little has been found in the literature about the c erbB 2 protein in human astrocytic tumors . ^^^ In the present study , we evaluated the expression of EGFR and c erbB 2 protein in 33 astrocytic tumors with immunohistochemistry . ^^^ The coexpression of EGFR and c erbB 2 protein was found in 17 ( 15 . 5 % ) of 33 tumors . ^^^ The results emphasize that the overexpression of EGFR parallels astrocytoma progession and higher frequency of c erbB 2 immunoreactivity was seen in snaplastic astrocytomas and glioblastomas than in low grade astrocytomas . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
METHODS : Southern blot , PCR / SSCP and DNA sequencing techniques were used in 33 gastric carcinomas to detect c met , EGFR , c erbB 2 , AKT 2 , c Ha ras , p 53 , p 16 and nm 23 H1 , for the presence of amplification , deletion , mutation and rearrangement . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Epidermal growth factor receptor ( EGF R ) and the oncogene product of c erbB 2 have been shown to be expressed in human tumors and in some cases relate to clinical outcome . ^^^ Epidermal growth factor receptor ( EGF R ) and the oncogene product of c erbB 2 have been shown to be expressed in human tumors and in some cases relate to clinical outcome . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Multivariate analysis of DNA ploidy , p 53 , c erbB 2 proteins , EGFR , and steroid hormone receptors for short term prognosis in breast cancer . ^^^ BACKGROUND : Several molecular genetic alterations in breast cancer , including aneuploidy , aberrant expression of p 53 , c erbB 2 , and EGFR have been associated with poor prognosis in breast cancer particularly in lymph node negative patients . ^^^ On the same specimens steroid hormone receptors ( ER and PR ) were measured in cytosol fraction using Abbott ELIZA assays , c erbB 2 and EGFR were determined in the tissue homogenate and mutant p 53 protein in the nuclear fraction by Oncogene Science ELISA procedures . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Tissue and serum c erbB 2 and tissue EGFR in breast carcinoma : three years follow up . ^^^ Expression of these protooncogenes results in production of epidermal growth factor receptor ( EGFR ) and c erbB 2 . ^^^ In the present work , tissue EGFR and c erbB 2 were determined in the membrane fractions of histopathologically verified malignant and normal tissues from the same breast of 94 patients . ^^^ Follow up , although short , of pre operative serum c erbB 2 showed a prognostic value ( P = 0 . 007 ) better than that of tumor size ( P = 0 . 04 ) , EGFR ( P = 0 . 18 ) , nodal involvement ( P = 0 . 25 ) and tissue c erbB 2 ( P = 0 . 85 ) . ^^^ The present work did not reveal any correlation between tissue , serum c erbB 2 or EGFR on one hand and age , menopausal status , stage , histological type and grade of carcinomas and nodal involvement on the other hand . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
SPECIFIC OBJECTIVE : The Epidermal Growth Factor Receptor ( EGFR ) is a specific cell membrane receptor that shows homology to the product of the oncogene c erbB 2 in human breast cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Identification of epidermal growth factor receptor and c erbB 2 pathway inhibitors by correlation with gene expression patterns . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
By means of LSAB and ABC techniques , the expressions of p 53 , c erbB 2 , EGFR and ras were examined on 75 cases of gastric cancer ( GC ) specimens . ^^^ Results : ( 1 ) The positive rate of p 53 , c erbB 2 , EGFR and ras expression was 41 . 3 % , 18 . 7 % , 61 . 3 % and 46 . 7 % , respectively . ^^^ Positive correlation was found between EGFR expression and degree of malignancy of GC . ( 2 ) No correlation was found between the expression of c erbB 2 and EGFR . ( 3 ) The expression of ras correlated positively with EGFR expression , but negatively with c erbB 2 ( P < 0 . 05 ) . ( 4 ) No correlation was found between the expression of p 53 and other genes examined . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The results showed that TGF beta 1 could inhibit mRNA expression of TGF beta 1 gene and that of c myc , EGFR and c erbB 2 genes in HO 8910 cells in vitro . ^^^ However , EGF could enhance the mRNA expressions of c myc , c erbB 2 and EGFR to various extents , but inhibit that of TGF beta 1 gene . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In 20 30 per cent of human breast cancers , the receptor tyrosine kinases epidermal growth factor receptor ( EGFR ) and c erbB 2 are overexpressed . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The relationship between bcl 2 , p 53 and tumour vascularization and epidermal growth factor receptor ( EGFR ) and c erbB 2 expression was also studied . ^^^ Tissue sections from resected tumour specimens of 107 NSCLC patients were evaluated immunohistochemically for vascular grade and bcl 2 , p 53 , EGFR and c erbB 2 expression . bcl 2 expression was found in 20 / 107 ( 19 % ) cases and was associated with squamous cell histology ( p = 0 . 03 ) . ^^^ No relationship was found between p 53 and EGFR expression and bcl 2 , c erbB 2 or vascular grade . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We report on the determination of the gene dosages of egfr and c erbB 2 in relation to the intratumoral concentration of the tyrosine kinase receptor protein EGFR and p185c erbB 2 and the clinical outcome of breast cancer patients in a retrospective study . ^^^ Prognostic unfavorable subgroups were determined in a life table analysis by ( a ) an average gene copy number of egfr of less than 0 . 4 and greater than 1 . 6 and an intratumoral EGFR concentration of more than 56 fmol / mg , ( b ) an intratumoral p185c erbB 2 concentration above 26 HNU / mg and ( c ) a quotient of egfr and c erbB 2 average gene copy numbers of less than 0 . 15 and greater than 4 . 35 . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The expression of the c erbB 2 , c erbB 3 and c erbB 4 members of the epidermal growth factor receptor family was examined in 16 fresh frozen tissue specimens of SCCHN using avidin biotin complex immunohistochemistry , with monoclonal and / or polyclonal antibodies directed against each . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Overexpression of EGFR and c erbB 2 causes enhanced cell migration in human breast cancer cells and NIH3T3 fibroblasts . ^^^ Overexpression of EGFR and c erbB 2 frequently occurs in human breast cancers , correlating with poor prognosis . ^^^ Here we show that overexpression of EGFR and c erbB 2 in cell lines increases cell migration , an important step in metastasis formation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
BACKGROUND : The c erbB 2 gene codes for a putative transmembrane protein , similar in structure to the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunohistochemical markers which have been proposed as being related to likely tumour behaviour ( epidermal growth factor receptor , c erbB 2 protein , oestrogen and progesterone receptors , cathepsin D , p 53 , and retinoblastoma protein ) do not distinguish screen detected from ' clinical ' cancers . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Fifty nine paraffin embedded astrocytic gliomas ( four WHO grade 1 , 21 WHO grade 2 , 17 WHO grade 3 and 17 glioblastomas , WHO grade 4 ) were immunohistochemically investigated for expression of transforming growth factor alpha ( TGF alpha ) , epidermal growth factor receptor ( EGF R ) and oncoprotein c erbB 2 by semiquantitative assessment . ^^^ There was no expression of EGF R and c erbB 2 in the majority of low grade astrocytomas . ^^^ Likewise , indices of EGF R and c erbB 2 positive cells correlated significantly . ^^^ Less significant correlations were also seen between EGF R , c erbB 2 frequencies and the Ki 67 labeling index . ^^^ Furthermore , besides EGF R and c erbB 2 , other growth factors and their receptors or mutant EGF R might participate in the proliferative activity of gliomas . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Androgen independent basal cell re epithelialization , c erbB 2 mRNA expression and androgen dependent EGFr mRNA expression in benign prostatic hyperplasia explant cultures treated with finasteride . ^^^ We have analyzed the effects of the 5alpha reductase inhibitor , finasteride ( MK 906 ) , on the mRNA expression of the epidermal growth factor receptor and c erbB 2 genes , in benign prostatic hyperplasia explant cultures treated with testosterone and with testosterone plus finasteride . ^^^ Using a semi quantitative reverse transcription polymerase chain reaction technique , we observed a significant decrease in expression of the epidermal growth factor receptor in the cultures treated with finasteride whereas no effect of finasteride on c erbB 2 transcription was detected , although the expression of both genes was increased by dihydrotestosterone . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Matrix metalloproteinase expression in human breast cancer : an immunohistochemical study including correlation with cathepsin D , type 4 collagen , laminin , fibronectin , EGFR , c erbB 2 oncoprotein , p 53 , steroid receptors status and proliferative indices . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The overexpression of two growth factor receptors epidermal growth factor receptor ( EGFR ) and c erbB 2 was evaluated immunohistochemically in malignant and benign ovarian neoplasms , considering the stage of the disease and histology of tumors . ^^^ The comparison of EGFR and c erbB 2 reactivity in tissue sections and respective cyst and / or ascitic fluid cells was also performed . c erbB 2 expression was detected in 44 . 4 % of ovarian carcinomas , and in benign neoplasms there was no evidence of its staining , while EGFR reactivity was found both in malignant ( 58 . 7 % ) and benign ( 50 % ) tumors . ^^^ Significant heterogeneity of staining was observed , however , the relationship between EGFR and c erbB 2 expression in tissue sections and cyst and / or ascitic fluid cells in individual patients was evident . ^^^ The c erbB 2 oncoprotein was detected more frequently in III / IV than in I / II stages according to the criteria of the International Federation of Gynecology and Obstetrics ( FIGO ) and the EGFR expression was independent of the clinical advancement of the disease . ^^^ The coexpression of c erbB 2 and EGFR was shown in 32 % of ovarian carcinomas , and it dominated in cases with FIGO stages III / IV . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We examined amplification of the c met , c erbB 2 , and epidermal growth factor receptor ( EGFR ) gene in the patients with primary gastric cancer , and compared the data with clinical features in order to clarify the relationship between oncogenic abnormality and clinical features . ^^^ Seven of the seventy cancers ( 10 . 0 % ) had c met gene amplification , nine ( 12 . 9 % ) had c erbB 2 gene amplification , and six ( 8 . 6 % ) had EGFR gene amplification , respectively . ^^^ Amplification of the c met , c erbB 2 and epidermal growth factor receptor gene in human gastric cancers : correlation to clinical features . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Estimation of EGFR and c erbB 2 protein immunoreactivity showed a significantly stronger staining with NSCLC and was correlated to the poor differentiation of the tumors , undergoing an aggressive biological behavior and an unfavorable prognosis . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In order to investigate the relationships of expression and tyrosine phosphorylation of cadherin catenin molecules and expression of growth factor receptor tyrosine kinase with loose cell to cell adhesion , immunohistochemical staining for E cadherin , alpha and beta catenin , phosphorylated tyrosine residues and tyrosine kinase receptors , including c erbB 2 , epidermal growth factor receptor ( EGF R ) , c met and K sam , in 17 undifferentiated and 10 differentiated type human gastric cancers was performed . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
They comprise epidermal growth factor receptor ( EGFR ) , c erbB 2 , c erbB 3 , and c erbB 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Expression of epidermal growth factor receptor family proteins ( EGFR , c erbB 2 and c erbB 3 ) in gastric cancer and chronic gastritis . ^^^ The expression and coexpression of EGFR , c erbB 2 and c erbB 3 in 21 gastric cancers and 20 chronic gastritis was examined using immunohistochemistry on fresh frozen tissues considering clinicopathological variables . ^^^ Generally , gastric cancer patients showed a higher incidence of EGFR , c erbB 2 and d erbB 3 overexpression than the group with chronic gastritis ( 81 % and 43 % ; 38 % and 45 % ; 35 % and 20 % , respectively ) , however , statistically significant differences were found only for EGFR expression ( p = 0 . 01 ) . ^^^ EGFR and c erbB 3 proteins were detected more frequently in patients with III / IV than in I / II of TNM stages , while c erbB 2 overexpression was higher in I / II vs . ^^^ The enhancement of c erbB 2 and c erbB 3 reactivity seems to cooperate with EGFR activation in the gastric cancer development . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Cell surface density of p 185 ( c erbB 2 ) determines susceptibility to anti p 185 ( c erbB 2 ) ricin A chain ( RTA ) immunotoxin therapy alone and in combination with anti p 170 ( EGFR ) RTA in ovarian cancer cells . ^^^ In cell lines that overexpressed p 185 ( c erbB 2 ) and also expressed p 170 ( EGFR ) , anti p 185 ( cerbB 2 ) RTA and anti p 170 ( EGFR ) RTA immunotoxins exerted synergistic cytotoxicity . ^^^ Importantly , tumor cells that had survived first treatment with anti p 185 ( c erbB 2 ) RTA alone still retained sensitivity to repeat treatment with the same immunotoxin and also proved susceptible to the synergistic cytotoxicity of anti p 185 ( cerbB 2 ) RTA in combination with anti p 170 ( EGFR ) RTA . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The HER 2 proto oncogene ( also known as neu or c erbB 2 ) belongs to the epidermal growth factor receptor family . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Proliferation , cell cycle , total amount of DNA , area of cell nucleus , as well as epidermal growth factor receptors ( EGFR ) and expression of oncogene C erbB 2 mRNA of Chinese breast cancer cell line ( BCaP 37 ) after being treated with kappa selenocarrageenan were determined by cell culture technique , image cytometry ( ICM ) and northern blot to explore its anti tumor mechanism . ^^^ Levels of EGFR and expression of C erbB 2 mRNA were significantly inhibited in cells treated with 60 mg / L selenocarrageenan . ^^^ It suggests that selenocarrageenan can inhibit proliferation of breast cancer cells through regulation of the levels of EGFR and expression of C erbB 2 mRNA . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We show here that following treatment with the progestin , R 5020 , breast cancer cells undergo a `` biochemical shift ' ' in the regulation of epidermal growth factor ( EGF ) stimulated signaling pathways : R 5020 potentiates the effects of EGF by up regulating EGFR , c ErbB 2 and c ErbB 3 receptors , and by enhancing EGF stimulated tyrosine phosphorylation of signaling molecules known to associate with activated type 1 receptors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Increases of as much as 49 fold compared to parental levels were observed in transforming growth factor alpha , epidermal growth factor receptor , c erbB 2 , and / or c erbB 3 mRNA expression in 14 of the 17 resistant sublines . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Expression of epidermal growth factor receptor ( EGFR ) or of c erbB 2 in primary breast cancer has been shown to predict for a poor chance of subsequent response of recurrent / metastatic disease to endocrine therapy . ^^^ None of the 18 pretreatment samples from patients who responded to therapy expressed c erbB 2 , and 1 of 18 expressed EGFR . ^^^ Of the nonresponders , 7 of 18 expressed EGFR pretreatment , and 4 of 18 expressed c erbB 2 ( 1 patient expressed both receptors ) . ^^^ Results confirmed previous findings that when considered independently , expression of either receptor pretreatment tended to predict for a poor chance of response ( EGFR , P = 0 . 046 ; c erbB 2 , P = 0 . 11 ) . ^^^ Importantly , patients who were either EGFR positive and / or c erbB 2 positive had a much poorer chance of response than `` double negatives ' ' ( response rates of 1 of 11 and 17 of 25 , respectively ; P = 0 . 0039 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Molecular pathology may play an important role in predicting the tumor prognosis , particularly p 53 , epidermal growth factor receptor ( EGFR ) , and c erbB 2 . ^^^ We investigated six variables ( age , sex , histopathological grade , p 53 , EGFR , and c erbB 2 ) to identify the role of such factors in predicting the outcome of patients with supratentorial astrocytic tumors . ^^^ Prognostic evaluation in supratentorial astrocytic tumors using p 53 , epidermal growth factor receptor , c erbB 2 immunostaining . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
AIMS : The c erbB 2 proto oncogene encodes a transmembrane protein which is highly homologous to epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
An immunohistochemical technique was used to evaluate the association between expression of c erbB 3 and clinical parameters and tumour markers such as epidermal growth factor receptor ( EGFR ) , c erbB 2 , cathepsin D and p 53 in archival formalin fixed paraffin embedded tumour tissues . ^^^ A significant relationship ( P < 0 . 05 ) was observed between strong immunoreactivity of c erbB 3 protein and histological grade , EGFR and cathepsin D , but not with expression of c erbB 2 , p 53 , oestrogen receptor status , lymph node metastases or age of patient . ^^^ We have also documented that a high percentage of EGFR ( 67 % ) , c erbB 2 ( 67 % ) , p 53 ( 75 % ) and cathepsin D positive DCIS ( 60 % ) were strongly positive for c erbB 3 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In this study , we immunohistochemically examined the expression of VEGF , nuclear and wild type cytoplasmic p 53 , bcl 2 , epidermal growth factor receptor , and c erbB 2 oncoprotein ; vascular grade ; proliferation index ; and extent of necrosis in non small cell lung cancer ( NSCLC ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
While the data about EGFR , c erbB 2 , c erbB 3 and phosphotyrosine are largely in line with what has been reported , we found the c erbB 4 protein expression to be decreased in the malignant tumours . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunohistochemical expression of c erbB 2 oncoprotein and EGF R in pre and postmenopausal breast cancer . ^^^ Tissues from 40 cases each of premenopausal and postmenopausal breast cancer were studied immunohistochemically for epidermal growth factor receptor ( EGF R ) and c erbB 2 oncoprotein . ^^^ In the premenopausal group , immunopositivity for c erbB 2 was 15 % and for EGF R 22 . 5 % , whereas in the postmenopausal group , 45 % of cases were positive for c erbB 2 and 42 . 5 % for EGF R . ^^^ A significant correlation was observed between the concomitant expression of c erbB 2 as well as EGF R and lymph node involvement . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
This peptide is homologous with a region in epidermal growth factor receptor ( EGFR ) and human oncogene c erbB 2 , and contains the ATP binding motif that is common among protein kinases . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Sixty prostatic TURP ( transurethral resection of the prostate ) specimens exhibiting atypical adenomatous hyperplasia ( AAH ) and / or prostatic intraepithelial neoplasia ( PIN ) lesions were assayed by immunohistochemistry for androgen receptor ( AR ) , epidermal growth factor receptor ( EGFR ) , c erbB 2 , transforming growth factor alpha ( TGF alpha ) , vascular endothelial growth factor ( VEGF ) , fibroblast growth factor 2 ( FGF 2 ) , MIB 1 , E cadherin , and high molecular weight keratin . ^^^ A similar growth factor and receptor profile was demonstrated in the secretory epithelium of high grade PIN and carcinoma with a tendency to higher expression of membranous EGFR and c erbB 2 and cytoplasmic TGF alpha , and lower levels of FGF 2 than in low grade PIN or BPH glands . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
MUC 1 ( episialin ) expression in non small cell lung cancer is independent of EGFR and c erbB 2 expression and correlates with poor survival in node positive patients . ^^^ AIM : To examine tumour samples immunohistochemically for MUC 1 ( episialin ) , epidermal growth factor receptor ( EGFR ) , and c erbB 2 , since the disruption of the cell cell adhesion system by MUC 1 and the c erbB oncoprotein family is known to be important in the development of metastasis in human cancers . ^^^ METHODS : 93 tumour samples from patients with early stage non small cell lung cancer treated with surgery alone were examined for episialin , EGFR , and c erbB 2 . ^^^ No correlation was observed between episialin and EGFR or c erbB 2 expression . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The type 1 family of growth factor receptors , which consist of the epidermal growth factor receptor , c erbB 2 , c erbB 3 , and c erbB 4 , are expressed in normal breast ductal epithelial cells and in some breast cancers . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
An immuno histochemical study including correlation with cathepsin D , extracellular matrix components , p 53 , Rb , bcl 2 , c erbB 2 , EGFR and proliferation indices . ^^^ The immunohistochemical expression of CD 44 in a series of 110 colorectal carcinomas and 25 adenomas was examined using the monoclonal mouse anti human phagocytic glycoprotein 1 , CD 44 ( clone DF 1485 ) in correlation with the expression of basement membrane ( BM ) antigens ( type 4 collagen , laminin ) , fibronectin , cathepsin D , p 53 , Rb , bcl 2 , c erbB 2 , EGFR , proliferation indices ( Ki 67 , PCNA ) and with other conventional clinicopathological variables . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
CONCLUSION : It is suggested that the aberration of c erbB 2 , p21ras , EGF and EGFR might be the early events in the initiation and progression of gliomas , whereas p 53 is involved in all stages of these tumors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Using the digoxin labelled probes and DNA RNA in situ hybridization technique , the expression of C erbB 2 and EGFR mRNA in routine paraffin sections of 30 human nasopharyngeal carcinomas ( NPC ) , 20 pericarcinomatous tissues ( PCT ) and 16 chronic inflammatory mucosae . ^^^ The results showed the positive rates of C erbB 2 and EGFR mRNA expression were 86 . 7 % , 83 . 3 % respectively in NPC and 80 . 0 % , 70 . 0 % in PCT , while those in chronic inflammatory mucosae were no detected . ^^^ In the PCT , the positive rates of C erbB 2 and EGFR mRNA in the atypic hyperplasia were higher than that in the simple hyperplasia , the amount of the positive cells of these two genes increased steadily in the mild , moderate and severe dysplasia and diffused from basal lamina of epithelium to the whole epithelium . ^^^ The results suggest that the activation of C erbB 2 and EGFR genes is an early event and play a synergic role in the carcinogenesis of NPC and examination of their expression is helpful in early diagnosis . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
It also specifically inhibited kinase activity of the protein ( IC 50 = 370+ / 120 pM ) , blocked EGF stimulated autophosphorylation of the receptor in cells ( ic 50 approximately 5 nM ) , inhibited cell proliferation ( IC 50 = 31 125 nM ) primarily in a cytostatic manner in cell lines that overexpress EGF R or c erbB 2 , and profoundly blocked the growth of a tumor that overexpresses EGF R in nude mice ( when given orally at 80 mg / kg / day for 10 days , daily ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In tumors from 136 patients with stage 1 and 2 cancer of the uterine cervix , the expression of epidermal growth factor receptor ( EGFR ) , c erbB 2 / neu , p 53 , and murine double minute 2 ( MDM 2 ) was studied using immunohistochemistry . ^^^ In 32 cases , amplification of EGFR , c erbB 2 / neu , MDM 2 , and c myc was studied by Southern blot hybridization . ^^^ Moderate / strong expression of EGFR was observed in 54 % of tumors . c erbB 2 / neu was focally positive in 12 cases . p 53 showed moderate / strong expression in 32 % of the tumors . ^^^ Gene amplification was found for EGFR ( four cases ) , c erbB 2 / neu ( two cases ) , and c myc ( six cases ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Messenger RNA ( mRNA ) encoding EGFR , c erbB 2 , and c erbB 3 , but not c erbB 4 , was detected in primary cultures of human bronchial epithelial cells , as well as in the human bronchial epithelial derived cell lines H 292 and 16HBE 14o . ^^^ The patterns of staining for c erbB 2 and c erbB 3 in the bronchial epithelium were similar to those for EGFR . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The positive rates of transforming growth factor ( TGF ) alpha , epidermal growth factor receptor ( EGFR ) and c erbB 2 were 45 . 7 % , 47 . 1 % and 92 . 3 % respectively . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Tumor suppressor genes ( p 53 , p 16 ) , oncogenes ( c erbB 2 , H ras , K ras , cyclin D 1 , src ) , and growth factor / receptor ( TGF alpha , EGFR ) seem to cause the malignant transformation of Barrett ' s esophagus . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
OBJECTIVE : To evaluate p 53 , epidermal growth factor receptor ( EGFR ) and c erbB 2 oncogene expression and compare it with microvessel count ( MVC ) in determining the clinical outcome of stage Ib squamous cell carcinoma ( SCC ) of the cervix . ^^^ STUDY DESIGN : Immunostaining with p 53 , EGFR , C erbB 2 and factor 8 antibodies was performed on tumor sections from 22 patients ( 11 with cancer recurrence , 11 free of cancer after four years ) . ^^^ CONCLUSION : The expression of EGFR , p 53 and c erbB 2 appears to have little prognostic value in stage Ib SCC of the uterine cervix . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Correlation between EGFR and c erbB 2 oncoprotein status and response to neoadjuvant chemotherapy in cervical carcinoma . ^^^ Prior to chemotherapy , quantitative tissue levels of epidermal growth factor receptor ( EGFR ) and c erbB 2 oncogene protein were measured by using an enzyme linked immunosorbent assay ( ELISA ) . ^^^ Tumor size prior to neoadjuvant chemotherapy did not show any correlation with either the concentrations of EGFR or c erbB 2 oncoprotein . ^^^ As well , the tumor reduction index did not manifest any correlation with EGFR , it did had an inverse linear correlation with the c erbB 2 oncoprotein levels ( Rs = 0 . 71 , P < 0 . 05 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunohistochemical localization of metallothionein in human breast cancer in comparison with cathepsin D , stromelysin 1 , CD 44 , extracellular matrix components , P 53 , Rb , C erbB 2 , EGFR , steroid receptor content and proliferation . ^^^ The MT expression was studied in comparison with the expression of the basement membrane ( BM ) antigens ( type 4 collagen , laminin ) , fibronectin , cathepsin D , adhesion molecule CD 44 , p 53 protein , the pRb , c erbB 2 oncoprotein , EGFR , stromelysin 1 , proliferation indices ( Ki 67 , PCNA ) , steroid receptor content as well as with other conventional clinicopathological parameters of breast cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunohistochemical evaluation of cathepsin D expression in colorectal tumours : a correlation with extracellular matrix components , p 53 , pRb , bcl 2 , c erbB 2 , EGFR and proliferation indices . ^^^ CD expression was correlated with the expression of extracellular matrix components ( collagen type 4 , laminin and fibronectin ) , p 53 protein , pRb , bcl 2 , c erbB 2 , EGFR , proliferation indices ( Ki 67 , PCNA ) as well as with other conventional clinicopathological features . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
I . ) and epidermal growth factor receptor ( EGFR ) content in sixty four patients with NSCLC . c erbB 2 and EGFR quantification were carried out from tissue homogenates using quantitative ELISA procedures . p 53 alterations were determined by immunohistochemical ( IHC ) detection with the monoclonal antibody DO 7 and analysis for p 53 mutations on exons 4 to 8 by single strand conformation polymorphism ( SSCP ) . ^^^ C erbB 2 expression and its relationship with ploidy , p 53 abnormalities and epidermal growth factor receptor content in human non small cell lung cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The HER 2 / neu ( also known as c erbB 2 ) oncogene is the second member of the epidermal growth factor receptor family . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We have reported that the transformation of human lung epithelial cells by c erbB 2 also requires an active ErbB 1 ( EGF receptor ) and the autocrine production of its ligand , TGF alpha . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The epidermal growth factor receptor family consists of four closely related transmembrane receptors : epidermal growth factor receptor ( EGF R ) , c erbB 2 , c erbB 3 , and c erbB 4 . ^^^ Based on the finding that EGF R and c erbB 2 form highly active transmembranous heterodimers that enhance cell growth and proliferation , we used Northern blot analysis and immunohistochemistry to analyze the concomitant expression of EGF R , c erbB 2 , and c erbB 3 in tissue samples obtained from 39 patients undergoing esophagectomy for esophageal cancer . ^^^ Immunohistochemical analysis showed weak EGF R , c erbB 2 , and c erbB 3 immunostaining in the normal esophageal tissue . ^^^ In esophageal cancer samples , immunoreactivity for EGF R , c erbB 2 , and c erbB 3 was mainly located in the cancer cells . ^^^ Strong EGF R , c erbB 2 , and c erbB 3 immunoreactivity was present in 59 % , 64 % , and 64 % of the esophageal cancer samples , respectively . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Tumors with tenascin expression and AI > or = 1 . 5 % significantly prevailed among MB with metastatic dissemination , whereas expression of c erbB 2 oncoprotein and epidermal growth factor receptor was found to be more typical for cases with local tumor recurrence . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We measured neovascularization , epidermal growth factor receptor , and c erbB 2 expression in a consecutive series of 233 surgically resected axillary lymph node negative breast cancer patients with a long term follow up to define the usefulness of these parameters as independent prognostic indicators of overall survival ( OAS ) . ^^^ Epidermal growth factor receptor and c erbB 2 expression were evaluated by immunohistochemistry . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Cell lines with c erbB 2 and EGFR expression and transphosphorylation activity display a high transendothelial invasiveness in an endothelial extracellular matrix model mimicking a capillary vessel wall in vitro . ^^^ Tyrosine phosphorylated c erbB 2 receptors and EGFR are localized predominantly in areas of the cell with high membrane extension activity . ^^^ Our data strongly suggest that c erbB 2 , especially in a heterodimer with EGFR , is closely involved in signaling pathways , inducing alterations in cell morphology that are required for a human breast cancer cell to become motile and conceivably metastatic . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
This cell system was developed previously as a model for lung adenocarcinoma by overexpression of c erbB 2 in nontumorigenic , T antigen immortalized HBECs . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Members of the epidermal growth factor receptor family of tyrosine kinases , including epidermal growth factor receptor , c erbB 2 ( HER 2 ) , c erbB 3 ( HER 3 ) , and c erbB 4 ( HER 4 ) , can be coexpressed at different levels in nonhematopoietic tissues . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The authors compared the expression of the epidermal growth factor receptor ( EGFR ) and c erbB 2 and c erbB 3 by Northern blot , in situ hybridization , and immunohistochemistry . ^^^ RESULTS : In papilla of Vater cancer , Northern blots showed comparable EGFR and c erbB 2 mRNA expression but significantly lower c erbB 3 mRNA levels than in normal papilla . ^^^ In pancreatic cancer , mRNA expression was enhanced compared with normal controls for EGFR ( 4 fold ) , c erbB 2 ( 2 . 5 fold ) , and c erbB 3 ( 5 . 2 fold ) . ^^^ In pancreatic cancer , immunostaining scores for EGFR , c erbB 2 , and c erbB 3 were significantly higher than controls . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunohistochemical co expression of c erbb 2 / Neu oncoprotein , altered tumour suppressor ( p 53 ) protein , EGF R and EMA in histological subtypes of infiltrating duct carcinoma of the breast . ^^^ Immunohistochemical staining of c erbB 2 ( Neu ) oncoprotein and mutant p 53 protein on 45 cases of infiltrating duct carcinoma ( IDC ) of the breast revealed 33 % membrane positivity of c erbB 2 oncoprotein , 46 % nuclear positivity of mutated p 53 protein , 33 % and 84 % membrane positivity of EGF R and EMA respectively . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The aim of this study was to study the protein expression of six proto oncogenes ( epidermal growth factor receptor ( EGFR ) , c fms , c myc , c kit , c erbB 2 and pan ras ) and one tumour suppressor gene ( TP 53 ) , by immunohistochemical staining of normal cervical stratified squamous epithelium and cervical intra epithelial neoplasia ( CIN ) . ^^^ These results suggest EGFR , c erbB 2 and c myc may be important proto oncogenes in CIN and that antibodies or anti genes targeted against them may alter the progress of CIN to invasive cancer . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
A preliminary study of CA 15 3 , c erbB 2 , epidermal growth factor receptor , cathepsin D , and p 53 in saliva among women with breast carcinoma . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
AIM : To investigate the role of metallothionein in colorectal tumours and the possible relation with other factors associated with tumour progression : expression of cathepsin D ( CD ) , CD 44 , p 53 , Rb , bcl 2 , c erbB 2 , epidermal growth factor receptor ( EGFR ) , proliferation indices ( Ki 67 , proliferating cell nuclear antigen ( PCNA ) ) , and conventional clinicopathological variables . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The Type 1 family of growth factor receptors includes epidermal growth factor receptor ( EGFR ) , c erbB 2 , c erbB 3 and c erbB 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We analyzed the expression of c Myc , c erbB 2 and epidermal growth factor receptor by immuno histochemistry in a group of 142 T ( 1 ) ( < 2 cm ) ductal breast carcinomas embedded in paraffin , previously studied for p 53 mutation and Bcl 2 over expression . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Herceptin binds to c erbB 2 , a member of the epidermal growth factor receptor family . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Basal growth of MCF 7 cells was unaffected by co administration of the growth factors EGF , TGF alpha , IGF 1 , and IGF 2 , and the new agents did not inhibit EGFR and c erbB 2 autophosphorylation in cell lysates from MDA 468 or SkBr 3 cells , respectively , suggesting that receptor tyrosine kinases are not targets for these compounds . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We have previously shown that HRG beta is mitogenic for various human mammary epithelial cell lines that coexpress c erbB 2 and c erbB 3 . ^^^ Phosphatidylinositol 3 kinase ( PI3K ) is activated by p 185 ( erbB 2 ) / erbB 3 heterodimers in cells stimulated by HRG , and PI3K is constitutively activated by p 185 ( erbB 2 ) / erbB 3 in breast carcinoma cells that overexpress c erbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
HER 2 / neu ( also known as c erbB 2 ) oncogene is a member of the epidermal growth factor receptor family and its amplification is one of the most common genetic alterations associated with human breast cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Comparative study of tumor angiogenesis and immunohistochemistry for p 53 , c ErbB 2 , c myc and EGFr as prognostic factors in gastric cancer . ^^^ The role of other prognostic factors in these tumors is still under investigation . 28 gastric dysplasia , 45 Early GC and 98 Advanced Gastric Cancers were evaluated for expression of the oncogenes p 53 , c ErbB 2 , c myc and the EGFr in paraffin embedded material utilizing Avidin Biotin immunohistochemistry techniques . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
When compared with carcinomas of a larger size , they were significantly associated with a lower histological grade ( SBR ) , a lower growth fraction ( Ki 67 antigen in less than 20 % of neoplastic cells ) and a lower number of positive cases ( more than 10 % of neoplastic cells ) as far as p 53 , c erbB 2 oncoproteins and EGF R , as detected by immunohistochemical methods , are concerned . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The expression of products of oncogens c erbB 2 and EGFR and proliferating antigens Ki 67 and PCNA in primary invasive ductal cancer of female breast . ^^^ The presence of the expression of oncoproteins c erbB 2 and EGFR , high index IP PCNA , Ki 67 and low levels of steroids receptors correlates with high histological malignancy ( Bloom III 0 ) ; 2 . ^^^ The lack of expression of oncoproteins c erbB 2 , EGFR and low index IP PCNA , Ki 67 correlates with high levels of steroids receptors ; 3 . ^^^ The expression of oncoprotein c erbB 2 and EGFR does not correlate with the diameter of tumour as well as with the involvement of axillary lymph nodes . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
A specific anti EGFR monoclonal antibody ( mAb ICR 62 ) inhibited MMP up regulation , migration and invasion induced by all three ligands , whereas an anti c erbB 2 mAb ICR 12 inhibited mitogenic and motogenic responses following ligand stimulation but had no effect on MMP expression . ^^^ The EGFR signalling pathway appears to be the dominant component controlling the proteolytic and invasive phenotype in HNSCC , whereas the c erbB 2 signalling pathway is responsible , in part , for the mitogenic and motogenic effects of ligands . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Overexpression of p 53 protein , epidermal growth factor receptor ( EGF R ) , and c erbB 2 protein was assessed by immunohistochemical staining of formalin fixed , paraffin embedded tissue from 64 invasive breast tumors . ^^^ Overexpression of p 53 , c erbB 2 and epidermal growth factor receptor in human breast carcinomas . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Functional links between over expression ( and occasionally mutational activation ) of c erbB 1 ( EGFR ) and c erbB 2 and specific phenotypes of metastatic cells have been elucidated . ^^^ Thirdly , both EGFR and c erbB 2 signalling can significantly upregulate specific matrix metalloproteinases , key enzymes involved in angiogenesis and invasion . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
It was established that there is no correlation between p 65 and c erbB 2 , EGFR or p 53 expression . ^^^ In low differentiated tumors ( grade 3 ) high p 53 index and high EGFR and c erbB 2 expression was connected with low p 65 expression . ^^^ The lack of c erbB 2 and EGFR and low p 53 expression was combined usually with high p 65 oncoprotein levels . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Because the c erbB 2 oncogene has extensive structural homology to the epidermal growth factor receptor gene , its overexpression can be expected to result in more aggressive tumour behaviour . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Therefore , the patterns of expression of the receptors , epidermal growth factor receptor ( EGF R ) , c erbB 2 , c erbB 3 , c erbB 4 , and one of the erbB ligands , heregulin ( HRG ) , were examined in normal and malignant breast cell lines and compared with expression of oestrogen receptor ( ER ) , a classical indicator of good prognosis . ^^^ There was an inverse correlation between ER and EGF R mRNA levels , as previously described , but no correlation between either of these receptors and c erbB 2 . c erbB 3 expression was positively correlated with ER . ^^^ Expression of antisense ER resulted in increased EGF R mRNA , demonstrating a functional link between the expression of these 2 genes , however , there was no significant change in c erbB 2 or c erbB 3 mRNA , suggesting that ER is not directly involved in control of expression of these genes . ^^^ A comparison of individual erbB receptors and HRG revealed that the majority of lines expressing increased levels of c erbB 2 also expressed elevated levels of c erbB 3 mRNA , and none of the cell lines that expressed both c erbB 2 and either c erbB 3 or c erbB 4 expressed the ligand HRG . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
A stepwise method was used to construct the models to define the best combination of risk factors among eleven prognostic factors : age , menopausal status , Scarff Bloom Richardson grade , clinical tumor size , pathological tumor size , estrogen and progesterone receptor status , urokinase type plasminogen activator , p 53 protein level , c erbB 2 protein and epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The expression of cytoplasmic c erbB 2 , epidermal growth factor receptor ( EGFR ) , proliferating cell nuclear antigen ( PCNA ) and dipeptidylpeptidase 4 ( DPP 4 ) was significantly higher in sporadic cancer of the right than of the left colon . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
A phosphopeptide antiserum raised against Smad 2 phosphoserine 240 reacted with Smad 2 in vivo when coexpressed with Cam kinase 2 and by activation of the platelet derived growth factor receptor , the epidermal growth factor receptor , HER 2 ( c erbB 2 ) , and the TGF beta receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunoreactivity for EGF R , TGF alpha , p 53 and c erbB 2 with paraffin embedded carcinoma tissue was investigated using labeled streptavidin biotin methods . ^^^ Positive rates of carcinoma cells were 27 % , 33 % , 32 % and 26 % for EGF R , TGF alpha , p 53 and c erbB 2 , respectively . ^^^ By univariate analysis , significant differences in overall survival and disease free survival were noted according to the co expression of EGF R and TGF alpha ( p < 0 . 0001 , p < 0 . 0001 ) , co expression of EGF R and c erbB 2 ( p = 0 . 0029 , p = 0 . 0028 ) , nodal status ( p = 0 . 0028 , p = 0 . 0001 ) , tumor size ( p = 0 . 0001 , p < 0 . 0001 ) and c erbB 2 expression ( p = 0 . 0034 , p = 0 . 018 ) , respectively . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
OBJECTIVE : The aim of this study was to analyze the correlation between expression of E cadherin complex proteins , epidermal growth factor receptor ( EGFR ) , and c erbB 2 and disease outcome in advanced stage ovarian carcinomas . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We measured the expression of the type 1 growth factor receptor gene family [ epidermal growth factor receptor ( EGFR ) , c erbB 2 , c erbB 3 and c erbB 4 ] in a series of 365 unselected primary breast cancers . ^^^ EGFR and c erbB 2 were inversely correlated to the presence of estradiol receptors ( ER ) and progesterone receptors ( PgR ) , and positively correlated to the histoprognostic grading ( HPG ) . ^^^ The expression level of EGFR and c erbB 2 was significantly higher in ER and PgR negative tumors compared with ER and PgR positive tumors ( Student ' s t test ) , and in tumors with higher grade compared with tumors with lower grade . ^^^ This study confirms that EGFR expression and c erbB 2 expression are markers of tumor aggressiveness in breast cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
RESULTS : Messenger RNA encoding the EGF receptors ( EGFR ) c erbB 2 and c erbB 3 , but not c erbB 4 , was detected in primary cultures of human nasal epithelial cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Serum level and tissue expression of c erbB 1 and c erbB 2 proto oncogene products in patients with squamous cell carcinoma of the head and neck . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The aim of this study was to evaluate c erbB 2 overexpression by means of a quantitative biochemical technique in 488 primary breast cancer patients with long term follow up ( median , 10 years ) and its relation to other biochemical prognostic factors ( uPA , p 53 , and epidermal growth factor receptor ) and adjuvant therapy . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Several prognostic indices in breast cancer , including c erbB 2 , epithelial growth factor receptors ( EGFR ) , estrogen and progesterone receptors are signal transduction molecules . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunohistochemical expression of Bcl 2 protein in breast lesions : correlation with Bax , p 53 , Rb , C erbB 2 , EGFR and proliferation indices . ^^^ Expression of bcl 2 protein was investigated and correlated with Bax , p 53 and Rb proteins , c erbB 2 , EGFR and the proliferation indices PCNA , Ki 67 and MIB 1 as well as with the conventional clinicopathological parameters in 95 cases for breast cancer tissue and 20 cases of benign hyperplastic lesions . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Tissues from 100 cases of breast cancer were analysed immunohistochemically for the presence of adrenocorticotropic hormone ( ACTH ) or ACTH like peptides and expression of c erbB 2 oncoprotein , epidermal growth factor receptor ( EGF R ) as well as oestrogen receptor ( ER ) . ^^^ Immunopositivity for ACTH was found in 15 % cases of infiltrating duct carcinoma of the breast , whereas 38 % and 36 % breast tumours were positive for c erbB 2 and EGF R respectively . ^^^ Further , a positive association between the immunoexpression of c erbB 2 and EGF R was noticed . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
One mechanism may be potentiation of angiogenesis , since upregulation of vascular endothelial growth factor ( VEGF ) expression by activation of epidermal growth factor receptor ( EGFR ) and / or c erbB 2 has been described . ^^^ The EGFR and c erbB 2 signaling pathway ( s ) plays a role in VEGF regulation in HNSCC , although EGFR would appear to be dominant in this cell type . . ^^^ An anti c erbB 2 mAb ( ICR 12 ) showed similar effects on basal or ligand modulated expression of VEGF in these cell lines , although to a lesser extent . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
These factors included tumor growth , stromal lymphocyte infiltration and fibrous tissue proliferation , degree of differentiation , Dukes stage , p 53 protein , c erbB 2 protein , P 21 protein , PCNA proliferation index and EGFR . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Overexpression of p 53 , EGFR , c erbB 2 and c erbB 3 in endometrioid carcinoma of the ovary . ^^^ OBJECTIVES : To determine overexpression of p 53 , EGFR , c erbB 2 and c erbB 3 in endometrioid carcinoma of the ovary and to evaluate the prognostic significance of these results , especially , coexisting overexpression of p 53 and one of the member of type 1 growth factor receptor family . ^^^ METHODS : Overexpressions of the p 53 , EGFR , c erbB 2 and c erbB 3 protein were studied by immunohistochemistry in paraffin embedded tumor tissue from 28 patients with endometrioid carcinoma of the ovary . ^^^ RESULTS : 11 ( 39 . 3 % ) , 13 ( 46 . 4 % ) , and 14 ( 50 . 0 % ) were stained positively with p 53 , c erbB 2 and c erbB 3 monoclonal antibodies . 13 ( 46 . 4 % ) was stained positively with EGFR polyclonal antibody . ^^^ There were no relationship between p 53 , EGFR , C erbB 2 , c erbB 3 and histologic grade , lymph node metastasis . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Overexpression of EGFR , c erbB 2 , c erbB 3 and c erbB 4 mRNAs was observed in 10 , 14 , 10 and 8 out of 15 head and neck cell lines respectively . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
RESULTS : After stimulation with EGF BT 474 , but not SK BR 3 , cells formed EGFR / c erbB 2 receptor complexes . ^^^ The induction of EGFR / c erbB 2 complexes in BT 474 was associated with shortening of the G 1 phase of the cell cycle . ^^^ In contrast , the concurrent activation of MAPK and PKB / Akt by EGF treatment led to an inhibition of proliferation in SK BR 3 and can be attributed to missing EGFR / c erbB 2 heterodimers . ^^^ Epidermal growth factor receptor , c erbB 2 and c erbB 3 receptor interaction , and related cell cycle kinetics of SK BR 3 and BT 474 breast carcinoma cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
RESULTS : In patients 55 years old or older , there was an association between increasing age at diagnosis and the presence of more favorable biologic characteristics of the tumor , including more tumors that express steroid receptors , lower proliferative rates , diploidy , normal p 53 , and absence of the expression of epidermal growth factor receptor and c erbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ERalpha negative breast tumors tend to overexpress growth factor receptors such as epidermal growth factor receptor or c erbB 2 . ^^^ Similar studies performed with MCF 7 cells overexpressing epidermal growth factor receptor or c erbB 2 confirmed that hyperactivation of MAPK resulted in down regulation of ERalpha that was reversible by MEK inhibition or transfection with dominant negative ERK 1 and ERK 2 constructs . ^^^ These data suggest that the hyperactivation of MAPK in epidermal growth factor receptor or c erbB 2 overexpressing breast cancer cells is directly responsible for generation of an ERalpha negative phenotype and , more importantly , that this process may be abrogated by inhibiting these pathways , thus restoring ERalpha expression . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The expressions of c erbB 2 , epidermal growth factor receptor ( EGFR ) and pan ras in normal cervical glands ( n=45 ) , glandular dysplasia / adenocarcinoma in situ ( GIN / ACIS ) ( n=32 ) and invasive cervical adenocarcinoma ( n=78 ) were determined and correlated with clinical prognosis . ^^^ The expressions of c erbB 2 , EGFR and pan ras in GIN / ACIS lesions and invasive tumours were significantly higher than in normal glands ( p < 0 . 001 ) , whereas there was no significant difference between expressions in GIN / ACIS lesions and invasive tumours , except for EGFR ( p=0 . 016 ) . ^^^ Significantly more normal glands adjacent to adenocarcinoma showed moderate / strong expressions for EGFR than c erbB 2 ( p=0 . 007 ) whereas significantly more GIN / ACIS lesions showed moderate / strong expressions for c erbB 2 than EGFR ( p=0 . 008 ) . ^^^ No correlation was found between moderate / strong expressions for c erbB 2 , EGFR or pan ras and stage at presentation ( p=0 . 384 , 0 . 056 , 0 . 842 respectively ) or with survival ( p=0 . 58 , 0 . 19 , 0 . 26 respectively ) . ^^^ In conclusion , EGFR is more important in inducing dysplastic change / malignant transformation whereas c erbB 2 plays a more significant role in tumour progression and invasion . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Using DNA flow cytometry and immunohistochemical staining techniques we determined the DNA content and the level of co expression of seven tumor associated proteins : proliferating cellular nuclear antigen ( PCNA ) , epidermal growth factor receptor ( EGFr ) , p 53 , c erbB 2 , H ras , c myc , and nm 23 . ^^^ In conclusion , this study demonstrates that the DNA content and genetic markers c myc , c erbB 2 , EGFr , H ras , p 53 , PCNA , and nm 23 do not predict survival after potentially curative resection of hepatic metastases from CRC . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunostaining for epidermal growth factor receptor ( EGFR ) , c erbB 2 , c erbB 3 , c erbB 4 , ER , and PR was performed in 107 cases of primary breast carcinomas from Anyang , China . ^^^ The expression rates of EGFR , c erbB 2 , c erbB 3 and c erbB 4 in this series were 43 . 9 % , 36 % , 27 % , and 45 . 8 % , respectively , and a stronger c erbB 4 staining of `` normal ' ' glandular structures inside tumors and in the vicinity of tumor clusters was confirmed . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Evaluation of the epidermal growth factor receptor ( EGFR ) and c erbB 2 in superspreading type and penetrating type gastric carcinoma . ^^^ The expression of epidermal growth factor ( EGF ) , epidermal growth factor receptor ( EGFR ) , transforming growth factor alpha ( TGF alpha ) , and of c erbB 2 was immunohistochemically investigated in resected gastric carcinoma ( in 39 cases of superspreading type and in 11 cases of penetrating type ) , to understand the differential biological features of these two types of gastric carcinoma . ^^^ EGF , EGFR and c erbB 2 positive cases were preferentially found in penetrating type rather than in superspreading type ( p < 0 . 05 , p < 0 . 01 , and p < 0 . 05 , respectively ) . ^^^ The positive rates of EGFR and c erbB 2 were significantly higher in submucosal gastric carcinoma than in intramucosal gastric carcinoma ( p < 0 . 01 , p < 0 . 05 , respectively ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Moreover , DCIS of the comedo type utilises type 1 tyrosine kinase growth factors , such as epidermal growth factor receptor ( EGFR ) and c erbB 2 , in receptor signalling for growth . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
A direct association of CA 9 expression with epidermal growth factor receptor , c erbB 2 , and MUC 1 expression was also noted ( P < 0 . 04 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
For example , c erbB 2 encodes the human epidermal growth factor receptor 2 ( HER 2 ) , which is overexpressed or amplified or both in several human malignancies including breast , ovarian , and colon cancers . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The c erbB 2 oncogene encodes a tyrosine kinase that constitutes the internal and transmembrane part of the epidermal growth factor receptor ( EGFR ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
BACKGROUND : c erbB 2 is a transmembrane signaling molecule closely related in structure to the epidermal growth factor receptor ( EGFR ) but biologically distinct from it . c erbB 2 has been implicated in cell transformation and tumor pathogenesis , but very little is known about its content and clinical significance in colorectal cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
EGFR family expression in breast carcinomas . c erbB 2 and c erbB 4 receptors have different effects on survival . ^^^ By immunohistochemistry , 36 % , 27 % , 26 % , and 82 % of the tumours were positive for EGFR , c erbB 2 , c erbB 3 , and c erbB 4 . ^^^ Statistical analysis of EGFR family members in these tumours showed a significant association between c erbB 2 expression and reduced disease free and cancer specific survival . c erbB 4 expression was associated with a more favourable outcome . ^^^ Co expression of c erbB 2 and EGFR was associated with a worse prognosis . c erbB 4 expression , however , showed an antagonistic effect on the clinical influence of c erbB 2 expression . ^^^ In conclusion , c erbB 2 expression in breast carcinomas is associated with an unfavourable clinical course and EGFR expression has a synergistic effect . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
High expression of epidermal growth factor receptor ( EGFR ) , c erbB 2 or c erbB 3 was associated with an infiltrating mode of invasion , nodal metastases and advanced pathological stages . ^^^ EGFR and c erbB 2 levels were strongly correlated ( P=0 . 0004 0 . 029 ) with the expression of MMP 2 , MMP 7 , MMP 9 , MMP 10 , MMP 11 , MMP 13 , VEGF A and VEGF C whereas the levels of c erbB 3 and B 4 showed a weaker correlation ( P=0 . 049 0 . 01 ) with some MMPs and VEGF C . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Of the tumors 48 % were immunoreactive for EGFR , 63 % for c erbB 2 , 78 % for c erbB 3 , 95 % for c erbB 4 , 88 % for estrogen receptor ( ER ) and 80 % for progesterone receptor ( PR ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Homotypic aggregation , target organ colonization , cell proliferation and apoptosis , expression of c erbB 2 , EGFR , p 53 and mucin , CA 19 9 and CEA of tumor cells of these 3 cell lines were comparatively studied by using three dimensional spheroid cell culture , TUNEL and immunocytochemistry . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
METHODS : Immunohistochemistry was used to compare expression of EGFR , c erbB 2 , c erbB 3 , epidermal growth factor , heparin binding epidermal growth factor like growth factor , and transforming growth factor alpha in bronchial biopsy specimens from normal and asthmatic subjects . ^^^ Changes in EGFR , c erbB 2 , and c erbB 3 distribution were measured by means of immunocytochemistry , whereas tyrosine phosphorylation was measured by means of immunoprecipitation and Western blotting . ^^^ In scrape wounded epithelial monolayers , tyrosine phosphorylation of EGFR , c erbB 2 , and c erbB 3 occurred immediately after damage ; however , only EGFR showed a change in expression in response to damage . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
OBJECTIVE : To explore the effect of expression of epidermal growth factor receptor ( EGFR ) , transforming growth factor beta ( TGF beta ) , c erbB 2 oncogene in myoepithelioma and malignant myoepithelioma . ^^^ The activated c erbB 2 oncogene , that is similar with EGFR in structure , plays an important promoting role in unrestricted progression of malignant myoepithelioma cells . . ^^^ Significance of expression of epidermal growth factor receptor , transforming growth factor beta , c erbB 2 oncogene in myoepithelioma of salivary gland ] . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In this first ever study , we investigated the role of nine prognostic markers ' expression ( estrogen receptor [ ER ] , progesterone receptor [ PR ] , p 53 , C erbB 2 , epidermal growth factor receptor [ EGFR ] , cathepsin D [ CD ] , proliferating cell nuclear antigen [ PCNA ] , DNA ploidy , and S phase fraction [ SPF ] ) and disease outcome in IBC cases compared with the control group . ^^^ The expression of nine prognostic markers , that is , ER , PR , p 53 , C erbB 2 , EGFR , CD , PCNA , SPF , and DNA ploidy , was studied by immunohistochemistry and flow cytometry . ^^^ Among p 53 , C erbB 2 , EGFR , and CD in the IBC group , only p 53 showed a significant correlation , with 70 % positivity in IBC versus 48 % positivity in the control group ( p < 0 . 05 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The human proto oncogene c erbB 2 / neu gene , which is structurally similar to the epidermal growth factor receptor gene , encodes a transmembrane protein of 185 kDa ( p 185 ) with tyrosine kinase activity . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
METHODS : The tumor samples from 97 primary ESCC patients with potentially curative resection were evaluated for the following parameters : tumor size , grade of differentiation , pattern of invasion , depth of invasion , degree of lymphocyte infiltration , lymph node metastasis , TNM stage and p 53 , EGFR , c erbB 2 , nm 23 , cathepsin D protein expression . ^^^ However , the multivariate Cox analysis demonstrated that only pattern of invasion ( RR = 2 . 000 ) , degree of lymphocyte infiltration ( RR = 0 . 509 ) , TNM stage ( RR = 1 . 733 ) , EGFR expression ( RR = 1 . 812 ) and c erbB 2 expression ( RR = 2 . 364 ) were significant prognostic factors ( P < 0 . 05 , respectively ) . ^^^ CONCLUSION : For ESCC , the pattern of invasion , degree of lymphocyte infiltration , EGFR and c erbB 2 protein expression had independent prognostic values as well as the TNM stage . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunohistochemical assay of p 53 , cyclin D 1 , c erbB 2 , EGFr and Ki 67 proteins in HPV positive and HPV negative cervical cancers . ^^^ The purpose of the present study was to analyse clinical correlation between HPV type 16 and 18 infection , expression of p 53 , cyclin D 1 , Ki 67 , c erbB 2 and EGFr gene products in cervical cancer cells as well as their nuclear ploidy . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In 10 cases of Barrett adenocarcinoma , samples from 8 tumor areas ( including superficial and deep from peripheral and central areas ) and a regional lymph node metastasis were studied for amplification of c myc , c erbB 2 , and EGFR . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The molecular mechanisms and signaling circuitry underlying these phenomena are now being elucidated . c erbB 2 , although having no known soluble ligand , is transactivated by heterodimerization with other family members ( EGFR , c erbB 3 , c erbB 4 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Comparison of the immunohistochemical expression of EGFR , c erbB 2 and p 53 protein between primary and recurrent breast cancer . ^^^ PATIENTS AND METHODS : The immunohistochemical expression of epidermal growth factor receptor ( EGFR ) , c erbB 2 and p 53 protein were analyzed on both primary and matching recurrent lesions from 42 patients with breast cancer . ^^^ RESULTS : EGFR and c erbB 2 expression were concordant between the primary and matching recurrent lesion in 27 ( 90 % ) of 30 cases in which EGFR was evaluated and in all ( 100 % ) 12 cases in which c erbB 2 was evaluated . ^^^ CONCLUSION : EGFR and c erbB 2 immunoreactivity were concordant between the primary and matching recurrent lesions in the majority of the breast cancer cases . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
EGFR , c erbB 2 and p 53 protein in the primary lesions and paired metastatic regional lymph nodes in breast cancer . ^^^ METHODS : Immunohistochemical analyses for epidermal growth factor receptor ( EGFR ) , c erbB 2 and p 53 protein were performed on the primary lesions and matching metastatic regional lymph nodes of 107 breast cancers . ^^^ RESULTS : EGFR , c erbB 2 and p 53 protein showed a concordance between the primary lesions and matching regional lymph nodes in terms of a negative or positive finding ( + and ++ ) in 98 ( 92 % ) of 106 cases , 76 ( 100 % ) of 76 cases and 79 ( 93 % ) of 85 cases respectively , while EGFR , c erbB 2 and p 53 protein also showed a concordance in the intensity of the immunoreactivity in 24 ( 89 % ) of 27 cases 14 ( 74 % ) of 19 cases and 30 ( 94 % ) of 32 cases respectively . ^^^ In 21 of 24 cases which showed a disconcordance in the positivity or the intensity of the positivity of EGFR , c erbB 2 and p 53 protein , one of the primary lesions and matching regional lymph nodes showed heterogeneous or 10 50 % immunostaining . ^^^ CONCLUSIONS : The immunoreactivity of EGFR , c erbB 2 and p 53 protein shows a concordance between the primary lesions and matching metastatic regional lymph nodes in a majority of breast cancers . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Candidate prognostic biomarkers for breast cancer include elevated proliferation indices such as Ki 67 and proliferating cell nuclear antigen ( PCNA ) ; ER and PR overexpression ; markers of oncogene overexpression such as c erbB 2 , TGF a and EGFr ; indicators of apoptotic imbalance including overexpression of bcl 2 and an increased bax / bcl 2 ratio ; markers of disordered cell signaling such as p 53 nuclear protein accumulation ; alteration of differentiation signals such as overexpression of c myc and related proteins ; loss of differentiation markers such as TGF b 2 receptor and retinoic acid receptor ; and alteration of angiogenesis proteins such as VEGF overexpression . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
It has been shown in a cell culture system that activation of c erbB 2 , but not the epidermal growth factor receptor , results in a DCIS like phenotype . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The c erbB 2 gene and its products ( also designated HER 2 and c neu ) encode for a 185 kd transmembrane glycoprotein with intracellular tyrosine kinase activity . c erbB 2 belongs to the epidermal growth factor receptor family , of which there are four known members , and has molecular homology to the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Induction of cancer cell migration by epidermal growth factor is initiated by specific phosphorylation of tyrosine 1248 of c erbB 2 receptor via EGFR . ^^^ In contrast , c erbB 2 / EGFR expressing cells displayed baseline transient calcium oscillations after EGF treatment due to short term PLC gamma 1 tyrosine phosphorylation and short term IP 3 and DAG turnover . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
One of the most studied onco gene families in breast tumors is the type 1 protein tyrosine kinase family , which consists of EGFR , c erbB 2 , c erbB 3 , and c erbB 4 . ^^^ Overexpression of c erbB 2 protein / mRNA in breast carcinomas is consistently associated with poor prognosis , while EGFR overexpression has been confirmed to have a synergistic clinical effect on the c erbB 2 influence . ^^^ Unlike other type 1 protein tyrosine kinases , expression of c erbB 4 protein / mRNA is reduced in carcinomas compared with that in normal breast epithelia , and its expression has also been associated with a better clinical outcome , indicating the need for c erbB 4 analysis when clinical therapeutic application of EGFR and c erbB 2 anitbodies is considered . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The neu ( c erbB 2 , HER 2 ) proto oncogene encodes a receptor tyrosine kinase that is a member of an important growth factor receptor family which includes the epidermal growth factor receptor ( EGFR , ErbB 1 ) , ErbB 3 and ErbB 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Pathology data were reviewed : 81 % of tumors were estrogen receptor positive , 74 % were progesterone receptor positive , 37 % overexpressed c erbB 2 , 30 % overexpressed p 53 , 79 % overexpressed Bcl 2 , 51 % overexpressed cyclin D 1 , and 39 % overexpressed epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Using the tissue microarray technique , 166 breast cancer cases , all characterized by comparative genomic hybridization , were evaluated by immunohistochemistry , using 15 different antibodies ( estrogen receptor , progesterone receptor , p 53 , Ki 67 , c erbB 2 , epidermal growth factor receptor , cyclins A , D 1 , and E , bcl 2 , p 21 , p 27 , Ck 5 / 6 , Ck 8 / 18 , and smooth muscle actin ) and chromogenic in situ hybridization for c erbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
To assess the significance of epidermal growth factor receptor family members , the overexpression of c erbB 1 and c erbB 2 was retrospectively investigated in 146 southern Iranian gastric cancer patients . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Both epidermal growth factor receptor ( EGFR ) and c erbB 2 mRNA and protein expression were increased in TAM R compared with wild type MCF 7 cells , whereas comparable levels of c erbB 3 mRNA and protein were expressed in both cell lines . ^^^ Under basal conditions , phosphorylated EGFR / c erbB 2 , EGFR / c erbB 3 but not c erbB2 / c erbB 3 receptor heterodimers were detected in TAM R cells in association with increased levels of phosphorylated extracellular signal regulated kinase 1 / 2 ( ERK1 / 2 ) . ^^^ These results demonstrate that TAM R MCF 7 cell growth is mediated by the autocrine release and action of an EGFR specific ligand inducing preferential EGFR / c erbB 2 dimerization and downstream activation of the ERK pathway . . ^^^ Elevated levels of epidermal growth factor receptor / c erbB 2 heterodimers mediate an autocrine growth regulatory pathway in tamoxifen resistant MCF 7 cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Amplification and / or overexpression of c erbB 2 , a receptor closely related to the EGFR , has been recently involved in prostate cancer progression . ^^^ We investigated EGFR and c erbB 2 expression in primary androgen dependent and in advanced androgen independent prostate cancer and their potential role as markers of disease progression . ^^^ EXPERIMENTAL DESIGN : EGFR and c erbB 2 expression were evaluated by immunohistochemistry in a consecutive series of 74 prostate cancer patients with the following characteristics : 29 patients ( group 1 ) treated with radical prostatectomy ; 29 patients ( group 2 ) treated with luteinizing hormone releasing hormone analogues and antiandrogen therapy followed by radical prostatectomy ; and 16 patients with hormone refractory metastatic disease . ^^^ In all patients we evaluated : association between EGFR and / or c erbB 2 expression and clinicopathological parameters ; and disease free survival according to EGFR and c erbB 2 expression in univariate analysis ( Kaplan Meier product limit method ) and in multivariate analysis ( Cox proportional hazards regression model ) . ^^^ RESULTS : EGFR expression was found in 12 of 29 ( 41 . 4 % ) group 1 patients , in 22 of 29 ( 75 . 9 % ) group 2 patients ( P < 0 . 0005 ) , and in 16 of 16 ( 100 % ) metastatic patients ( P < 0 . 005 ) , whereas c erbB 2 expression was found in 11 of 29 ( 37 . 9 % ) group 1 , in 10 of 29 ( 34 . 5 % ) group 2 patients , and in 9 of 16 ( 56 . 3 % ) metastatic patients . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ER , PR , p 53 , C erbB 2 , EGFR , Cathepsin D , PCNA , DNA ploidy and S phase fraction , were studied by immunohistochemistry and flow cytometry . ^^^ Among p 53 , C erbB 2 , EGFR and Cathepsin D in the test group , only EGFR showed a significant correlation , i . e . 33 % immunoreactivity in test cases and 19 % immunoreactivity in controls ( p < 0 . 05 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The type 1 growth factor receptors are a family of transmembrane receptors comprising epidermal growth factor receptor ( EGFR ) , c erbB 2 , c erbB 3 , and c erbB 4 . ^^^ Both EGFR and c erbB 2 are associated with poor prognosis in certain tumours . ^^^ RESULTS : There were several correlations between variables , and overexpression of EGFR , c erbB 2 , and c erbB 4 was found to be associated with adverse clinical outcome , although the results were significant only for c erbB 4 ( p = 0 . 002 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
BACKGROUND : Epidermal growth factor receptor ( EGFR or HER 1 ) and its homolog c erbB 2 ( HER 2 ) are membrane receptors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
BACKGROUND : Epidermal growth factor receptor ( EGFR ) and c erbB 2 are 2 of the 4 members of the erbB receptor family that play a role in signaling by forming heterodimers between family members . ^^^ METHODS : The immunohistochemical expression of EGFR and c erbB 2 was determined on 670 women who underwent operation for primary breast cancer . ^^^ RESULTS : According to the combination of EGFR and c erbB 2 , 670 patients were classified into 4 groups : EGFR ( ) / c erbB 2 ( ) ( 417 patients ) ; EGFR ( + ) / c erbB 2 ( ) ( 136 patients ) ; EGFR ( ) / c erbB 2 ( + ) ( 72 patients ) ; and EGFR ( + ) / c erbB 2 ( + ) ( 45 patients ) . ^^^ Univariate analyses on disease free and overall survival showed a significant difference among these 4 groups , whereas the difference between patients with positive and negative expression of EGFR was not statistically significant in patients with positive expression of c erbB 2 . ^^^ A multivariate analysis indicated the combination of EGFR and c erbB 2 to be an independently significant prognostic factor for disease free and overall survival . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The c erbB 2 proto oncogene encodes a 185kDa protein p 185 , which belongs to epidermal growth factor receptor family . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In the present study , we investigated the expression of three receptor tyrosine kinases , epidermal growth factor receptor ( EGFR ) , c erbB 2 , and c kit protein , by comparing surgically resected 40 LCNECs with other neuroendocrine ( NE ) lung tumors : 9 typical carcinoids ( TCs ) , 5 atypical carcinoids ( ACs ) , and 13 small cell lung carcinomas ( SCLCs ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
BACKGROUND : We recently confirmed , in a series of 365 human breast cancers , that EGFR and c erbB 2 were associated with estradiol receptors ( ER ) and / or progesterone receptors ( PgR ) negative tumors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In contrast , amplification of c erbB 2 in tumors results in dramatic overexpression and constitutive activation of the receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Distribution of prognostically unfavourable product of c erbB 2 oncogene and EGF R in carcinomas of the breast and uterine cervix . ^^^ A comparative study was undertaken between cancer of the uterine cervix ( n = 50 ) and female breast cancer ( n = 50 ) with reference to the expression of c erbB 2 oncoprotein ( HER 2 / neu ) and that of epidermal growth factor receptor ( EGF R ) , both being highly homologous structurally . ^^^ Expressions of EGF R and c erbB 2 oncoprotein were viewed in breast and cervical cancer tissues by immunochemical staining . ^^^ Cervical cancer cases showed much higher expression of EGF R which also revealed significant association with the expression of c erbB 2 oncoprotein and tumour grading . ^^^ Among breast cancer cases , over expression of EGF R correlated significantly with metastasis of lymph node ; and expression of c erbB 2 oncoprotein showed a significant relationship with histological grading of the tumour . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
On sections from both a human lung adenocarcinoma and a squamous cell carcinoma tissue microarray , fluorescence intensity for two epidermal growth factor receptors ( EGFR and c erbB 2 ) correlates with diagnostic pathologic assessment , indicating that immunohistochemistry quantitation can be achieved . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
BACKGROUND : Although the overexpression of the Epidermal Growth Factor Receptor 2 ( EGFR 2 , HER 2 / neu , c erbB 2 ) in malignancies might predict chemoresistance and poor prognosis , its clinical relevance has not been widely studied and determined in testicular tumors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
C erbB 2 protein is localized on the membrane surface and is classified in the EGFR family . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The findings were correlated with clinical parameters and the immunohistochemical ( IHC ) markers EGFR , c erbB 2 , c erbB 3 , Ki 67 and p 53 on cryostat sections . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The results showed that ( a ) inactivation of the quinazoline head by appending an N methylaniline group to its 4 position reduced EGFR tyrosine kinase ( TK ) inhibitory activity by ca . 200 fold and decreased the ability of the combi molecule to block serum induced growth stimulation in c erbB 2 transfected NIH3T3 cells by ca . 10 fold , ( b ) abrogation of the alkylating activity or the DNA damaging potential of the triazene tail by forming 3 , 3 dimethyltriazenes did not suppress EGFR TK inhibitory affinity but decreased the antiproliferative activity in basal growth assays , and ( c ) the antiproliferative activities of the monoalkyltriazenes that possessed binary EGFR TK inhibitory and alkylating activities were superior to those of their monotargeted counterparts . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Cryostat sections were stained with monoclonal antibodies against epidermal growth factor receptor ( EGFR ) , c erbB 2 , c erbB 3 , CD 82 , Ki 67 , p 120 , p 53 , bcl 2 , and CD 31 . ^^^ EGFR was raised in 32 , c erbB 2 in 29 , c erbB 3 in 46 , p 53 in 29 , bcl 2 in 26 , Ki 67 in 36 , p 120 in 46 , and CD 31 in 29 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The growth inhibitory effects of fulvestrant were associated with a decrease in basal EGFR , c erbB 2 and ERK1 / 2 activity in TAM R but not WT cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
BACKGROUND : Epidermal growth factor receptor ( EGFR ) and c erbB 2 are membrane receptors expressed in a variety of solid human cancers and directly correlated with poor prognosis . ^^^ The objective of this work was to evaluate the EGFR and c erbB 2 levels in non resectable gastric carcinomas , their possible relationship with a variety of clinicopathological tumor parameters , and their prognostic significance . ^^^ Membranous EGFR levels were examined by radioligand binding assays and cytosolic c erbB 2 levels by means of an immunoenzymatic assay . ^^^ RESULTS : There was a wide variability in EGFR ( 80 . 3 2910 fmol / mg of protein ) and c erbB 2 ( 0 . 4 10071 NHU / mg of protein ) levels in neoplastic tissues from patients with unresectable gastric carcinomas . ^^^ Statistical analysis showed that there was no relationship between tumor c erbB 2 or EGFR content and any other patient or tumor characteristics . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
OBJECTIVE : To detect the relations of c erbB 2 oncogene protein , epidermal growth factor receptor ( EGFR ) and transforming growth factor beta 1 ( TGF beta 1 ) to the progression or metastasis of pancreatic carcinoma . ^^^ METHODS : Using streptavidinbiotin complex ( SABC ) method , c erbB 2 oncongene protein , we examined immunohistochemically EGFR and TGF beta 1 expressions in wax tissue sections from 10 individuals with normal pancreas ( NP ) , 13 patients with chronic pancreatitis ( CP ) and 36 patients with pancreatic ductal adenocarcinoma ( PC ) . ^^^ The individual expression of c erbB 2 , EGFR and TGF beta 1 was not related to the age and sex of the patients as well as the site , size and histopathological grade of tumors ( P > 0 . 05 ) , but to the clinical stage of tumors ( P < 0 . 01 ) . ^^^ CONCLUSION : Detection of c erbB 2 oncogene protein , EGFR , and TGF beta 1 expressions in pancreatic tissue is helpful to judge the malignancy , progression , and metastasis of PC . . ^^^ Expression of c erbB 2 oncogene protein , epidermal growth factor receptor , and TGF beta 1 in human pancreatic ductal adenocarcinoma . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Different expression patterns of KIT , EGFR , and HER 2 ( c erbB 2 ) oncoproteins between epithelial and mesenchymal components in uterine carcinosarcoma . ^^^ To reveal the significance of the expression of tyrosine kinase receptor type oncoproteins in this tumor type , the incidence and distribution of the KIT , EGFR , and HER 2 ( c erbB 2 ) oncoproteins were immunohistochemically examined in 16 surgically resected cases . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The c erbB 2 gene codes for a membrane receptor protein that is homologous to the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The cells express androgen receptor ( AR ) , PSA , VEGF , EGFR , c erbB 2 , and TGFalpha . ^^^ Elevated EGFR ( membrane ) but not c erbB 2 expression was demonstrated in the TEN12F line only . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
All four known subgroups of the EGFR family were determined by immunohistochemistry ( IHC ) : c erbB 1 ( EGFR ) , c erbB 2 ( HER2 / neu ) , c erbB 3 ( HER 3 ) and c erbB 4 ( HER 4 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Coexpression of epidermal growth factor receptor ( EGFR ) and c erbB 2 in 47 68 % of ovarian cancer cells indicate their strong association with tumor formation . ^^^ We examined the effects of simultaneous antisense or immunosuppression of EGFR and c erbB 2 expression on the invasive phenotype , aneuploidy , and genotype of cultured human ovarian carcinoma cells ( NIH : OVCAR 8 ) . ^^^ We report here that suppression of both EGFR and c erbB 2 results in regression of aneuploidy and genomic imbalances in NIH : OVCAR 8 cells , restores a more normal phenotype , and results in a more normal gene expression profile . ^^^ Simultaneous suppression of epidermal growth factor receptor and c erbB 2 reverses aneuploidy and malignant phenotype of a human ovarian carcinoma cell line . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Additionally , overexpression of epidermal growth factor receptor and c erbB 2 , and loss of fibronectin were observed only in the HNGC 2 cell line , implicating the significance of these pathways in tumor progression . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We examined the potential of quantitative epidermal growth factor receptor ( EGFR , synonym : c erbB 1 ) and c erbB 2 ( synonym : HER2 / neu ) mRNA expression to predict minor or major histopathologic response to neoadjuvant radiochemotherapy ( cis platinum , 5 FU , 36 Gy ) , followed by radical surgical resection , in patients with oesophageal cancer . ^^^ Relative expression ( tumour / paired normal tissue ratio standardised for beta actin ) was calculated for EGFR and c erbB 2 mRNA . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Epidermal growth factor receptor 1 plasma membrane expression , assessed by immunohistochemistry on paraffin embedded tissues , was correlated with clinical parameters as well as immunohistochemical expression results of HER 2 ( c erbB 2 ) , BAX , BCL 2 , p 53 and anti Ki 67 , previously studied in the same series of patients . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Overexpression of c erbB 2 and EGF R proteins in radiation induced skin ulcers . ^^^ Immunohistochemical studies were performed on 72 radiation induced skin ulcer specimens using c erbB 2 and epidermal growth factor receptor ( EGF R ) protein antibodies . ^^^ We found that the overexpression rate of c erbB 2 oncoprotein was 59 . 7 % and of EGF R was 70 . 8 % . ^^^ It is suggested that the overexpression of c erbB 2 and EGF R proteins may be due to the poor healing of the radiation induced skin ulcers . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The expression of c myc , MDM 2 , c erbB 2 , EGFR , p 53 , p 14 ( ARF ) , p 16 ( INK 4 ) , p 21 ( WAF 1 ) and nm 23 was detected by immunohistochemical assay . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
C erbB 2 belongs to the human epidermal growth factor receptor ( tyrosine kinase receptor ) family that plays an important role in cell cycle regulation and differentiation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunohistochemistry was used to examine the status of proliferation activity with antibodies against Ki 67 and BM 28 , and the status of EGFR family members with antibodies against EGFR , c erbB 2 , and c erbB 4 . ^^^ Higher levels of EGFR and c erbB 2 expressions were more often observed in the poorly differentiated tumors , compared with that in the moderately differentiated tumors . ^^^ Poorly differentiated ovarian serous carcinomas express higher levels of Ki 67 , BM 28 , EGFR , and c erbB 2 proteins . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We have found that 20 . 1 and 31 . 8 % of cases were positive for EGFR and c erbB 2 , respectively , and 45 and 45 . 1 % of tumours overexpressed for c erbB 3 and c erbB 4 , respectively . ^^^ The expression of either EGFR or c erbB 2 was associated with other bad prognostic features and with poor outcome . ^^^ Patients whose tumours co expressed c erbB 2 and c erbB 3 , as well as those whose tumours co expressed EGFR , c erbB 2 and c erbB 4 showed an unfavourable outcome compared with other groups , while combined c erbB 3 and c erbB 4 expression was associated with a better outcome . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Amplification of the epidermal growth factor receptor ( EGFR ) and / or c erbB 2 oncogenes and overexpression of their proteins are detected in 30 % of gastric carcinomas , but there are few reports regarding the correlation between gene amplification and protein overexpression . ^^^ We examined the correlation between amplification of the EGFR and c erbB 2 genes , detected using fluorescence in situ hybridization , and overexpression of their proteins , detected using immunohistochemistry , in formalin fixed tissue sections of 54 surgically resected gastric carcinomas . ^^^ A mean EGFR gene copy number of 4 . 0 or more and / or an EGFR / CEP7 ratio of 1 . 7 and a mean c erbB 2 gene copy number of 7 . 0 or more and / or a c erbB 2 / CEP17 ratio of 2 . 0 or more would be useful in defining increased EGFR and c erbB 2 gene copy numbers , respectively , in gastric carcinomas . . ^^^ A proposal for diagnostically meaningful criteria to classify increased epidermal growth factor receptor and c erbB 2 gene copy numbers in gastric carcinoma , based on correlation of fluorescence in situ hybridization and immunohistochemical measurements . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Association between the response to gefitinib and the clinicopathological features or immunohistochemical expression of epidermal growth factor receptor ( EGFR ) , phosphorylated EGFR , or c erbB 2 were then investigated . ^^^ No other clinicopathological features or the expression of EGFR , phosphorylated EGFR , or c erbB 2 were associated with the response to gefitinib . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Expression of epidermal growth factor receptor and c erbB 2 oncoprotein in trophoblast populations of placenta accreta . ^^^ OBJECTIVE : The purpose of this study was to investigate the expression of epidermal growth factor receptor and c erbB 2 oncoprotein in trophoblast populations of placenta accreta . ^^^ STUDY DESIGN : Paraffin sections of 43 placental specimens with ( cases ) and 43 without ( controls ) placenta accreta were studied immunohistochemically for epidermal growth factor receptor and c erbB 2 expression in the syncytiotrophoblast , villous cytotrophoblast , and extravillous cytotrophoblast . ^^^ Epidermal growth factor receptor and c erbB 2 protein levels were also performed by Western blot analysis . ^^^ RESULTS : The percentage of strong / intermediate immunoreactivity of epidermal growth factor receptor in the syncytiotrophoblast was significantly higher in cases ( 98 % ) than controls ( 79 % ; odds ratio , 11 . 1 ; 95 % CI , 1 . 3 92 . 0 ; P = . 03 ) , although strong / intermediate immunoreactivity of c erbB 2 in the syncytiotrophoblast was significantly lower in cases ( 35 % ) than controls ( 81 % ; odds ratio , 0 . 1 ; 95 % CI , 0 . 1 0 . 3 ; P < . 001 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We examined KIT , EGFR , and c erbB 2 overexpressions immunohistochemically in 150 cases of surgically resected breast cancer and their correlation with the histological type and grade and mesenchymal and / or myoepithelial immunophenotype of primary tumors . ^^^ KIT , EGFR , and c erbB 2 overexpressions were detected in 15 ( 10 % ) , 12 ( 8 % ) , and 23 ( 15 % ) , respectively . ^^^ KIT and EGFR appeared to be indicators of high grade breast carcinoma groups that often contain the carcinomas with mesenchymal and / or myoepithelial differentiation , which are distinct from the group with c erbB 2 overexpression . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The human protooncogene c erbB 2 , also known as HER 2 / neu is sited on 17q21 chromosome and codifies a transmembranous glycoprotein of 185 KD , named c erbB 2 protein , with tyrosin kinasic activity and homologue from molecular point of view with the epidermal growth factor receptor ( EGFR ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Amplification and overexpression of the Her2 / neu ( c erbB 2 ) growth factor receptor occurs in approximately 25 % of early stage breast cancers . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Promising approaches and molecular markers include gene expression profiles , DNA ploidy , loss of heterozygosity and chromosomal aberrations as detected by CGH and FISH ( 1q , 17p , 17q ) , as well as oncogenes / tumor suppressor genes and their proteins ( TP 53 , PTEN , c erbB 2 , N myc , c myc ) , growth factor and hormonal receptors ( PDGFRA , VEGF , EGFR , HER 2 , HER 4 , ErbB 2 , hTERT , TrkC ) , cell cycle genes ( p 27 ) and cell adhesion molecules , as well as factors potentially related to therapeutic resistance ( multi drug resistance , DNA topoisomerase IIalpha , metallothionein , P glycoprotein , tenascin ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Potentially prognostic histopathological markers vary among different entities and consist of assessment of necroses , mitoses , differentiation , vascular proliferation , and growth pattern , whereas immunohistochemical features include proliferation markers ( Ki 67 , MIB 1 ) , expression of oncogenes / tumor suppressor genes and their proteins ( TP 53 , c erbB 2 ) , growth factor and hormonal receptors ( VEGF , EGFR , HER 2 , HER 4 , ErbB 2 ) , cell cycle genes ( p 27 , p14ARF ) and cell adhesion molecules , as well as factors potentially related to therapeutic resistance ( DNA topoisomerase IIalpha , metallothionein , P glycoprotein , tenascin ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Finally , survival of patients expressing EGFR and / or c erbB 2 was slightly shorter . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
RESULTS : EGF induced EGFR / EGFR and EGFR / c erbB 2 interactions correlate with stimulation of cell proliferation in BT 474 cells . ^^^ CONCLUSION : The growth inhibitory effect of Herceptin on c erbB 2 overexpressing breast cancer cells is considerably modulated by EGFR coexpression and consequently EGFR / c erbB 2 homo and heterointeractions , as well as the presence or absence of growth factors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The human epidermal growth factor receptor , type 2 ( HER 2 / neu or c erbB 2 ) is a 185 kDa transmembrane protein that is phosphorylated upon ligand binding and dimerization with members of the HER / c erbB family and regulates cell growth and differentiation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Amplification and overexpression of c erbB 2 , epidermal growth factor receptor , and c met in biliary tract cancers . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
BACKGROUND : Our objective was to examine the utility of endoscopic biopsy specimens in judging the status of epidermal growth factor receptor ( EGFR ) and c erbB 2 genes and proteins in the entire tumor . ^^^ METHODS : Endoscopic biopsy specimens and specimens of whole representative cut surfaces of corresponding surgically resected tumors were obtained from 14 patients with gastric carcinoma , and immunohistochemistry and fluorescence in situ hybridization were then performed to determine the protein expression and gene amplification profiles , respectively , of EGFR and c erbB 2 in these biopsy and surgical specimens . ^^^ All three cases with EGFR overexpression and all five cases with c erbB 2 overexpression showed intratumor heterogeneity with regard to their EGFR and c erbB 2 status , respectively . ^^^ Usefulness and limitation of multiple endoscopic biopsy sampling for epidermal growth factor receptor and c erbB 2 testing in patients with gastric adenocarcinoma . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In 32 cases of the undifferentiated type and 37 cases of the relatively differentiated types , we immunohistochemically examined the expressions of myoepithelial markers and KIT , epidermal growth factor receptor ( EGFR ) , and c erbB 2 oncoproteins . ^^^ In 11 ( 85 % ) of 13 cases with KIT overexpression , EGFR overexpression concurred . c erbB 2 overexpression was almost equally detected in both the undifferentiated and relatively differentiated types , and did not correlate with KIT or EGFR overexpression . ^^^ Phosphotyrosine was detected in 16 ( 67 % ) of 24 cases with KIT , EGFR , and / or c erbB 2 overexpression but only in six ( 18 % ) of 34 cases without KIT , EGFR , or c erbB 2 overexpression ( P = 0 . 0002 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The 185 kDa transmembrane glycoprotein human epidermal growth factor receptor 2 ( HER 2 ) ( p185 / neu , c ErbB 2 ) is overexpressed in breast and ovarian cancers . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
BACKGROUND : TGF alpha and c erbB 2 are important mediators of tumor neoangiogenesis linked to the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The HER 2 gene , also known as c erbB 2 or neu , is a proto oncogene that encodes a membrane bound receptor tyrosine kinase of the epithelial growth factor receptor ( EGFR ) family . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
A literature search was undertaken using PubMed and MEDLINE search engines , using the keywords p 53 , p 21 , p 16 , p 27 , SMAD 4 , K ras , cyclin D 1 , Bax , Bcl 2 , EGFR , EGF , c erbB 2 , HB EGF , TGFbeta , FGF , MMP , uPA , cathepsin , heparanase , E cadherin , laminins , integrins , TMSF , CD 44 , cytokines , angiogenesis , VEGF , IL 8 , beta catenin , DNA microarray , and gene profiling . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Monoclonal antibodies ( trastuzumab , gefitinib , erlotinib and bevacizumab ) targeting tissue markers and involved in tumor growth and metastasization ( EGFR , C erbB 2 , VEGF ) have been developed ; they showed therapeutical single agent activity as well as potent synergy with chemotherapy agents in metastatic cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
EGFR , c erbB 2 and ki 67 in NSCLC and preneoplastic bronchial lesions . ^^^ BACKGROUND : The relationships between EGF R and c erbB 2 with other factors involved in tumour regulation are not well understood . ^^^ MATERIALS AND METHODS : The presence of EGF R , c erbB 2 and Ki 67 was evaluated by immunohistochemistry in non small cell lung cancer ( NSCLC ) and preneoplastic lesions . ^^^ RESULTS : Forty two percent of the tumours were positive for EGF R , 22 % for c erbB 2 and 97 % for Ki 67 . ^^^ No statistically significant correlation was found between EGF R and Ki 67 , EGF R and c erbB 2 or between c erbB 2 and Ki 67 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
EGFR , pEGFR , and EGFRvIII expression did not correlate with any of the previously tested markers ( c erbB 2 , c erbB 3 , p 53 , ki 67 , and microvessel density ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The aim of this article was to review the expression of epidermal growth factor receptor ( EGFR ) , c erbB 2 , vascular endothelial growth factor ( VEGF ) and matrix metal loproteinases ( MMPs ) in HNSCC patients and to study their possible correlation to various clinicopathologic parameters . ^^^ Based on this review , the expression of EGFR , c erbB 2 , VEGF , or MMPs play important roles for tumor growth , invasion and metastasis in HNSCC . c erbB receptors , MMPs and VEGF might aid the clinician in the selection of an appropriate therapy for individual patients and help to predict the prognosis of patients . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In ERalpha tumors , overexpression of epidermal growth factor receptor ( EGFR ) or c erbB 2 , leading to increased growth factor signaling , is observed such that mitogen activated protein ( MAP ) kinase ( MAPK ) is significantly hyperactivated compared with ERalpha+ breast cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Does c erbB 2 play a role in the first steps of lung carcinogenesis . ^^^ C erbB 2 , another member of the erbB family , is overexpressed in lung carcinomas , suggesting that this mechanism may play a role in carcinogenesis . ^^^ We evaluated the correspondence between the morphological changes of the bronchial epithelium and the c erbB 2 expression . ^^^ Immunostaining was performed using anti c erbB 2 antibodies ( clone CBI ) . ^^^ CONCLUSION : C erbB 2 does not seem to be involved in the first step of carcinogenesis of squamous cell carcinoma . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The immunohistochemistry method was used to observe the number of G cells , the expression of protein of EGFR ( EGF receptor ) , C erbB 2 , p 53 , p 16 and bcl 2 in gastric tissue . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The neu proto oncogene encodes a protein highly homologous to the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The neu proto oncogene encodes a receptor tyrosine kinase ( p 185 ) that is closely related to the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We have compared the responses of serum inducible immediate early genes to ligand activation of the epidermal growth factor receptor ( EGFR ) or a hybrid EGFR / neu receptor containing the intracellular domain of the neu proto oncogene . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The rat neu proto oncogene , which is a putative growth factor receptor closely related to the epidermal growth factor receptor , can be activated in vivo by a single point mutation in the sequence encoding its transmembrane region . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
METHODS : The expression of c erbB 2 , p 53 , p16INK4A , p27KIP1 , cyclin D 1 and epidermal growth factor receptor ( EGFR ) was studied in a series of 137 primarily resected oesophageal adenocarcinoma samples . ^^^ CONCLUSION : The immunohistochemical expression of c erbB 2 oncoprotein , cylin D 1 , p16INK4A , p27KIP1 , p 53 and EGFR in most oesophageal adenocarcinomas suggests their implication in the pathogenesis of this entity . ^^^ Prognostic significance of expression patterns of c erbB 2 , p 53 , p16INK4A , p27KIP1 , cyclin D 1 and epidermal growth factor receptor in oesophageal adenocarcinoma : a tissue microarray study . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The torpedo ( top ) locus of Drosophila encodes the fruitfly homolog of the vertebrate epidermal growth factor receptor gene and the neu proto oncogene . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Serum starved NIH 3T3 cells expressing an epidermal growth factor receptor ( EGF R ) / neu construct encoding a hybrid receptor protein were stimulated with EGF and the activation of the neu tyrosine kinase and stimulation of growth factor inducible genes were followed at the mRNA , protein , and activity levels , and compared to the corresponding responses in the neu proto oncogene and oncogene expressing cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The Neu proto oncogene ( also called ErbB 2 and HER 2 ) encodes a tyrosine kinase transmembrane receptor homologous to the epidermal growth factor receptor ( EGF R ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The neu proto oncogene encodes a plasma membrane protein belonging to the epidermal growth factor receptor family . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In two cell lines that overexpress erbB 2 but do not expresss EGFR ( MDA MB 453 breast cancer cells and a Chinese hamster ovary cell line that had been transfected with erbB 2 ) , phosphorylation of p185erbB2 was induced only by gp 30 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The ability of AR to elicit in vivo phosphorylation of the EGF receptor ( EGFR ) and p185erbB2 was studied in four human epithelial cell lines which expressed either or both of the receptor tyrosine kinases . ^^^ AR induced the phosphorylation of the EGFR and p185erbB2 , and phosphoamino acid analysis revealed enhanced phosphorylation of tyrosine residues in both receptor proteins . ^^^ A monoclonal antibody ( mAb ) which binds to the extracellular domain of the EGFR blocked the phosphorylation of the EGFR and p185erbB2 as well as AR induced mitogenesis indicating that the EGFR mediated these responses . ^^^ Amphiregulin induces tyrosine phosphorylation of the epidermal growth factor receptor and p185erbB2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We selected two human cell lines differing in degree of expression of the p185erbB2 protein , which is closely related to EGF R . ^^^ On the contrary , it prolonged the EGF dependent EGF R and p185erbB2 ( 5 E ) tyrosine phosphorylation in p185erbB2 ( 5 E ) expressing cells . ^^^ Because tyrphostin has been shown to be an inhibitor of p185erbB2 and EGF R in vitro , this finding indicates that the tyrphostin effect on p185erbB2 ( 5 E ) and EGF R was the result of an indirect mechanism in transfected cells . ^^^ We conclude that whereas tyrphostins were designed to inhibit EGF R tyrosine kinase activity , under our conditions EGF R is not a physiological target for tyrphostin , nor is one of its related protein tyrosine kinases , p185erbB2 ( 5 E ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Furthermore , phospho p95ErbB2 forms heterodimers with ErbB 3 , but not EGFR , while p185ErbB2 heterodimerizes with both EGFR and ErbB 3 . ^^^ Inhibition of p95ErbB2 , p185ErbB2 , and EGFR phosphorylation by GW 572016 resulted in the inhibition of downstream phospho Erk1 / 2 , phospho AKT , and cyclin D steady state protein levels . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
All three cell lines expressed transforming growth factor alpha ( TGF alpha ) , epidermal growth factor receptor ( EGFR ) , c erb B 2 , and c met genes . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
To investigate the expression of c H ras ( p 21 ) , c erb B 1 ( EGFR ) and c erb B 2 ( p 185 ) gene products in human bladder cancer , immunohistochemical studies using monoclonal antibodies to these proteins were performed on formaline fixed ( within 15 hours ) paraffin sections of tumor tissues from 20 patients with bladder cancer , normal appearing adjacent bladder ( non tumor ) tissues from 11 of the 20 patients , and normal bladder tissues from 3 patients who died of non cancerous diseases as control . p 21 Positive staining was demonstrated in the superficial cells of urothelium in 1 of 3 controls , also in 5 of 20 tumor tissues compact cells without vacuole in cells which have an increased nuclear / cytoplasmic ratio . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In the search for sensitive and specific tumor markers for bladder carcinoma , expression of various oncogenes and gene products ( such as c erb B 2 , p 53 ) and epidermal growth factor receptor merits particular attention . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In addition to the EGF R , B 11 recognized two unidentified soluble proteins present in the cytoplasm of the SKBR 3 cell line but different from the c erb B 2 oncoprotein expressed by these cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The EGF independence of S 2 was accompanied by an overexpression of the mRNAs for epidermal growth factor receptor ( EGF R ) , transforming growth factor alpha , and c erb B 2 as compared to the EGF dependent subline ( S 1 ) . ^^^ Altered gene expression of c myc , epidermal growth factor receptor , transforming growth factor alpha , and c erb B 2 in an immortalized human breast epithelial cell line , HMT 3522 , is associated with decreased growth factor requirements . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Experimental systems employing transfection with eukaryotic expression vectors are described that are designed to test the hypothesis that overexpression of epidermal growth factor receptor or the related protein C ERB B 2 may confer an increased growth rate under conditions of estrogen deprivation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Similarity of protein encoded by the human c erb B 2 gene to epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Cytoplasmic expression of c myc protein was related to histological grade ( P = 0 . 005 ) , papillary status ( P = 0 . 007 ) , the S phase fraction ( P = 0 . 008 ) , the mitotic index ( P = 0 . 021 ) , overexpression of epidermal growth factor receptor ( P = 0 . 045 ) , and c erb B 2 ( P = 0 . 17 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The aim of this study was to evaluate the immunohistochemical expression of epidermal growth factor ( EGFR ) and c erb B 2 oncoprotein in a series of 71 hepatocellular carcinomas as well as in the adjacent hepatic tissue and to assess any correlation with HBsAg expression . ^^^ The immunohistochemical avidin biotin peroxidase complex ( ABC ) method was performed on formalin fixed paraffin sections for the detection of EGFR , c erb B 2 oncoprotein and HBsAg using monoclonal antibodies . ^^^ Our results suggest that both c erb B 2 oncoprotein and EGFR do not seem to be predominantly involved in the transformation of hepatocytes to the malignant phenotype . . ^^^ C erb B 2 oncoprotein and epidermal growth factor receptor in human hepatocellular carcinoma : an immunohistochemical study . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
C mel , c erb B 2 , c myc , c src 1 , p 53 , platelet derived growth factor A chain , gro , transforming growth factor alpha , epidermal growth factor receptor and tissue plasminogen activator were all expressed in at least some cell lines . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The impact of EGFR staining on patient survival was compared with tumor stage , histologic grade , immunoreactivity for c erb B 2 and proliferating cell nuclear antigen , flow cytometrically determined S phase fraction and DNA ploidy , abnormal expression of blood group related antigens , and patient blood type . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We examined HPV DNA typing and its gene expression , oncogenes ( c myc , EGF R , c erb B 2 ) and p 53 in cervical dysplasia and cancer with molecular biologic , immunohistochemical technique and binding assay to establish a gene diagnosis of uterine cervical cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Northern blotting also revealed the co expression of 5 . 6 kb EGF R mRNA and 4 . 6 kb c erb B 2 mRNA . ^^^ Co expression of epidermal growth factor receptor and c erb B 2 proto oncogene product in human salivary gland adenocarcinoma cell line HSG and the implications for HSG cell autocrine growth . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The presence of amplified c erb B 2 and epidermal growth factor receptor ( EGF R ) was examined in tumor cells present in bladder washings . ^^^ The authors detected amplified c erb B 2 and EGF R in cancer cells of cytologic Grade 2 and 3 tumors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Expression of estrogen receptor , progestin receptor , epidermal growth factor receptor , HER 2 / neu ( c erb B 2 ) oncoprotein , and cathepsin D were determined . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The HER 2 / neu proto oncogene ( also known as c erb B 2 ) is homologous with , but distinct from , the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In order to evaluate the growth and / or proliferative capabilities of cyst epithelia , epidermal growth factor ( EGF ) , epidermal growth factor receptor ( EGFR ) and c erb B 2 gene product were determined in cyst epithelia , adenoma and adenocarcinoma . ^^^ Immunohistochemical study in acquired cystic disease of the kidney expression of vimentin , epidermal growth factor , epidermal growth factor receptor and c erb B 2 gene product ] . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In this study , the expression of epidermal growth factor receptor ( EGFr ) and c erb B 2 was evaluated in 35 formalin fixed , paraffin embedded cases of transitional cell carcinomas of the urinary bladder ( TCCs ) . ^^^ EGFr and c erb B 2 expression was assessed with immunohistochemistry , and molecular analysis of the respective genes was performed with the differential polymerase chain reaction . ^^^ None of Ta / T1 TCCs cases showed strong expression against EGFr , in contrast to c erb B 2 where two cases ( 18 % ) were found to express an intense immunosignal . ^^^ Eleven ( 85 % ) T2 / T3 cases showed strong positivity either against EGFr or c erb B 2 ( P < 0 . 001 ) . ^^^ Eleven patients died within 12 months after the diagnosis , and all of them showed strong expression of EGFr and c erb B 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Epidermal growth factor ( EGF ) and transforming growth factor alpha ( TGF alpha ) stimulate cellular proliferation , whereas epidermal growth factor receptor ( EGFR ) and c erb B 2 oncoprotein are involved in the regulation of cellular growth . ^^^ The present study investigated the prognostic value of these growth factors ( EGF and TGF alpha ) and oncogene products ( EGFR and c erb B 2 ) in TCC UUT . ^^^ Immunohistochemically , EGF was recognized as positive in 50 . 4 % of the samples , TGF alpha in 27 . 8 % , EGFR in 41 . 3 % , and c erb B 2 oncoprotein in 6 . 8 % . ^^^ The immunoreactivity for EGF and c erb B 2 oncoprotein was significantly ( P < 0 . 05 ) correlated with both stage and grade , whereas TGF alpha correlated only with stage and EGFR only with grade . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
MATERIALS AND METHODS : EGF , transforming growth factor alpha ( TGF alpha ) , EGF receptor ( EGF R ) , and c erb B 2 were determined immunohistochemically in formalin fixed paraffin embedded tumor samples of 30 patients with locally confined RCCs . ^^^ On the contrary , there was a significant correlation between EGF and TGF alpha ( p < 0 . 001 ) , EGF and EGF R ( p = 0 . 028 ) , EGF R and c erb B 2 ( p = 0 . 0009 ) , and inversely related between TGF alpha and tumor stage ( p = 0 . 047 ) and between EGF R and malignancy grade ( p = 0 . 03 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In these cancerous tissues , no clear amplification of EGF r and c erb B 2 protein expression was observed . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunohistochemical staining for p 53 , MIB 1 , epidermal growth factor receptor ( EGFR ) , c erb B 2 , and bcl 2 have shown promise as prognostic factors when evaluated singly , although multivariate analyses that include histologic grade and the interactive effects of these markers have not been studied extensively . ^^^ METHODS : The authors evaluated 229 transitional cell carcinomas in 229 patients using the World Health Organization grading schema and immunohistochemical staining with antigen retrieval for p 53 , MIB 1 , EGFR , c erb B 2 , and bcl 2 , and they related these markers to invasion after controlling for grade with a multivariate logistic regression model . ^^^ Although neither EGFR nor c erb B 2 were as important as the other three markers in determining the risk of invasion , Grade 3 tumors that stained for one , and especially both , of these markers were less likely to be invasive . ^^^ CONCLUSIONS : These five markers sort into three interactive pairs : MIB 1 and p 53 , bcl 2 and p 53 , and EGFR and c erb B 2 . ^^^ Finally , EGFR and c erb B 2 related closely to each other and in Grade 3 tumors imply a lesser probability of invasion . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The immunohistological expression of p 53 and MDM 2 oncoproteins was examined in paraffin embedded tissue from 106 patients with transitional cell carcinoma of the urinary bladder and was related to various clinicopathological features , the expression of proliferation associated markers ( proliferating cell nuclear antigen PCNA and Ki 67 ) , c erb B 2 oncoprotein and epidermal growth factor receptor ( EGFR ) , as well as to survival . ^^^ C erb B 2 , EGFR and proliferation marker expression increased with grade , stage and non papillary configuration . ^^^ C erb B 2 expression and stage were the two independent predictors of disease free survival and Ki 67 LI and EGFR LI the independent predictors of post relapse survival . ^^^ The role of p 53 , MDM 2 and c erb B 2 oncoproteins , epidermal growth factor receptor and proliferation markers in the prognosis of urinary bladder cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The median of pO 2 values and the percentage of hypoxic areas ( pO 2 < 10 mmHg ) were calculated and correlated with the histological type , grading , ER , PR , and the expression of Ki 67 , p 53 , EGFR , pS 2 , and c erb B 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Cell surface expression of the following was examined : EGP 2 ; MUC 1 ; EGFr ; E and N cadherin ; the alpha 2 , alpha 3 , alpha 5 , beta 1 and beta 4 integrins ; c erb B 2 ; and N CAM . c erb B 2 was expressed in a higher percentage of the bone metastasizing MT 1 cells than the MA 11 cells , whereas E cadherin was expressed in MA 11 but not MT 1 cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Abnormal expression of TGF alpha , EGF R and c erb B 2 has been demonstrated in several human malignancies . ^^^ METHODS : The immunohistochemical expression of TGF alpha , EGF R , and c erb B 2 was studied in paraffin material of 62 clinical Wilms tumors . ^^^ RESULTS : Generally , TGF alpha , EGF R , and c erb B 2 were expressed in tissue of the normal kidney and at variable levels in the three cell types of Wilms tumor , i . e . , blastemal , epithelial , and stromal cells . ^^^ Immunoreactive blastema cells were found in 48 % , 44 % , and 34 % of tumors for TGF alpha , EGF R , and c erb B 2 , respectively . ^^^ It was found that TGF alpha , EGF R , and c erb B 2 blastemal and epithelial expression gradually increased from T 1 to T 3 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The amplification and overexpression of the human epidermal growth factor receptor 2 gene HER 2 ( also known as c erb B 2 or neu ) have been shown to be associated with bladder cancer and its progression . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Clinical , pathologic , and tumor marker ( p 53 , MIB 1 , bcl 2 , c erb B 2 , and epidermal growth factor receptor ) data were collected at baseline and during followup . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Using immunocytochemistry , tumors were immunostained for overexpression of p 53 , c erb B 2 , and epidermal growth factor receptor and were evaluated quantitatively for expression of estrogen receptor , progesterone receptor , and Ki 67 antigen , a marker of cellular proliferation . ^^^ Epidermal growth factor receptor , c erb B 2 , estrogen receptor , and progesterone receptor statuses did not differ significantly between the two groups . ^^^ CONCLUSION : Markers that did not correlate with survival included the hormone receptors , estrogen receptor and progesterone receptor , and the oncogenes , c erb B 2 and epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Our team used validated rabbit polyclonal antibodies which were raised against human EGFR and C erb B 2 , using the streptavidin peroxidase conjugate method . ^^^ Of interest was the finding that EGFR and C erb B 2 were colocalized as well as independently expressed by separate populations of NE cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Using immunocytochemistry , tumors were immunostained for overexpression of c erb B 2 , epidermal growth factor receptor ( EGFR ) , p 53 , and expression of the Ki 67 defined antigen ( a marker of cellular proliferation ) , tumor necrosis factor alpha ( TNFalpha ) , estrogen receptor ( ER ) , progesterone receptor ( PR ) , and P glycoprotein ( P 170 , a marker of multidrug resistance ) . ^^^ Expression of steroid hormone receptors , TNFalpha , and P glycoprotein and overexpression of c erb B 2 or EGFR are not associated with chemoresistance . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The HER 2 / neu gene or c erb B 2 , localized on chromosome 17q , belongs to a family of tyrosine kinase receptors and shares extensive homology with the epidermal growth factor receptor . c erb B 2 gene amplification and protein overexpression have been reported in several human cancers . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Recent studies evaluated the expression of molecular targets in salivary gland carcinomas ( c kit = 53 90 % , EGFR = 25 85 % , c erb B 2 = 11 58 % , p 53 = 11 67 % , H ras = 18 % ) ; these targets are very important since new targeted drugs are now available . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
OBJECTIVE : To examine the expression of c Met , c Erb b 2 ( HER2 / neu ) , and epidermal growth factor ( EGFR ) in a cohort of 12 chordomas , based on the current and future availability of targeted molecular inhibitors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
OBJECTIVE : To investigate prognostic significance of and correlations between HER 1 ( EGFR ) , HER 2 ( c erb B 2 ) , HER 3 ( c erb B 3 ) , HER 4 ( c erb B 4 ) , and phosphorylated Akt ( P Akt ) in patients treated with radiation for cervical carcinoma . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
DESIGN : We constructed a tissue microarray from 38 cases of IMC and performed immunohistochemical stainings for cytokeratin ( CK ) 7 , CK 20 , estrogen receptor , progesterone receptor , p 53 , c Erb B 2 , CD 34 , CK 5 , epidermal growth factor receptor , and c Kit in both MC and non MC components . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
EXPERIMENTAL DESIGN : In this study , a range ( n = 23 ) of markers [ pRb , p 16 , p 21 , p 27 , p 53 , proliferating cell nuclear antigen , cyclin D 1 , bcl 2 , epidermal growth factor receptor , C erb B 2 , topoisomerase 1 , liver fatty acid binding protein , matrix metalloproteinases ( MMP ) 1 3 , 7 , 9 , and 13 , MT 1 MMP , MT 2 MMP , and tissue inhibitors of MMP 1 3 ] of putative prognostic significance have been investigated by immunohistochemistry on formalin fixed , wax embedded sections in a series ( n = 90 ) of stage 3 ( Dukes C ) colorectal cancers . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The epidermal growth factor receptor ( EGFR ) and erbB 2 are expressed by NSCLC cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In particular , an EGFR related kinase , erbB 2 was much less efficient than EGFR at phosphorylating p 97 , p 56 , and p 23 and incapable of phosphorylating p 68 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The specificity of this effect was confirmed by showing that the antiproliferative effects of soluble erbB 2 extracellular domain were reversed by either p 75 or gp 30 . p 75 did not show binding to the epidermal growth factor receptor and had no growth effects on cells overexpressing epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The neu / HER 2 proto oncogene ( also called erbB 2 ) encodes a transmembrane glycoprotein related to the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
To address these issues , we utilized a chimeric molecule encompassing the extracellular domain of the epidermal growth factor ( EGF ) receptor ( EGFR ) fused to the transmembrane and intracellular domains of the erbB 2 product . ^^^ In this EGFR / erbB 2 chimera , erbB 2 kinase activity is regulated by EGF binding . ^^^ An EGFR / erbB 2 mutant bearing multiple Tyr Phe substitutions at erbB 2 autophosphorylation sites ( EGFR / erbB 2 5P ) displayed markedly reduced phosphotyrosine content following EGF stimulation in comparison with the non mutated chimera . ^^^ When expressed in NR 6 cells , the EGFR / erbB 2 5P mutant was unable to deliver a sizeable mitogenic signal when activated by EGF at physiological levels . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The epidermal growth factor ( EGF ) receptor ( EGFR ) and the erbB 2 gene product , gp185erbB 2 , exhibit distinct abilities to stimulate mitogenesis in different target cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We report the localization over the cell surface and the early steps of antibody induced internalization of the product of the erbB 2 proto oncogene , structurally related to the epidermal growth factor receptor ( EGFR ) . ^^^ Similar internalization is shown by a chimeric molecule EGFR / erbB 2 in response to EGF . ^^^ Both the timing and the pathway of internalization followed by the erbB 2 / p185 appear totally similar to those described for the EGFR . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Expression of epidermal growth factor receptor ( EGFR ) and ERBB 2 oncoprotein were studied in paraffin embedded normal ( n = 2 ) , hyperplastic ( n = 17 ) , and malignant ( n = 147 ) prostatic tissues by immunohistochemistry . ^^^ Expression of epidermal growth factor receptor and ERBB 2 ( HER 2 / Neu ) oncoprotein in prostatic carcinomas . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
There was a strong correlation between EGFR gene amplification and increased copies of the ERBB 2 gene on chromosome 17 , suggesting a synergistic selection for these two genes either during cancer progression or in culture . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
These genes include the epidermal growth factor receptor gene , erbB 2 , int 2 , hst , and H ras , which exert positive control over cell growth , as well as the suppressor genes Rb 1 , and the gene coding for p 53 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
By using chimeric molecules between EGFR and erbB 2 , we found that the determinants responsible for the specificity of mitogenic signal transduction are located in the amino terminal half of the tyrosine kinase domain of either receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The probes spanned the four major protein coding classes of oncogenes ; growth factor proteins ( csis ) ; growth factor receptor / tyrosine kinase related proteins [ erbB 1 ( epidermal growth factor receptor , EGF R ) , neu ( HER2 / neu , erbB 2 ) , mos , yes ] ; nuclear binding proteins ( c myc , c fos ) ; and guanosine 5 ' triphosphate binding proteins ( N ras , H ras ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Using a panel of somatic cell hybrids that segregate rat chromosomes , the localization of five cancer related rat genes was determined : ( 1 ) two thyroid receptor genes , THRA1 / ERBA1 and THRB / ERBA2 on chromosomes 10 and 15 respectively , ( 2 ) two ERBB genes , namely the epidermal growth factor gene ( EGFR , also called ERBB 1 ) and the ERBB 2 gene ( also designated neu ) on chromosomes 14 and 10 respectively , and ( 3 ) the retinoblastoma gene , RB 1 , on chromosome 15 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
All carcinomas in which tyrosine phosphorylated PLC gamma 1 was present also expressed detectable levels of the epidermal growth factor receptor or erbB 2 , two tyrosine kinases known to phosphorylate this enzyme . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
DNA ploidy pattern and amplification of ERBB and ERBB 2 genes in human gastric carcinomas . ^^^ The DNA ploidy pattern and amplification of ERBB and ERBB 2 genes were examined in paraffin embedded tissue from gastric carcinomas using flow cytometry and a slot blot hybridization technique . ^^^ Of the nine specimens having an aneuploid stem cell line in the primary tumor and / or in metastases , three showed ERBB 2 gene amplification and one showed ERBB gene amplification . ^^^ These findings indicate that aneuploidy is frequently associated with amplification of ERBB and ERBB 2 genes . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The erbB 2 gene product , gp185erbB 2 , unlike the structurally related epidermal growth factor ( EGF ) receptor ( EGFR ) , exhibits constitutive kinase and transforming activity . ^^^ We used a chimeric EGFR / erbB 2 expression vector to compare the mitogenic signaling pathway of the erbB 2 kinase with that of the EGFR , at similar levels of expression , in response to EGF stimulation . ^^^ The EGFR / erbB 2 chimera was significantly more active in inducing DNA synthesis than the EGFR when either was expressed in NIH 3T3 cells . ^^^ However , under conditions in which activation of the erbB 2 kinase induced DNA synthesis at least fivefold more efficiently than the EGFR , the levels of erbB 2 or EGFR induced tyrosine phosphorylation of PLC gamma and GAP were comparable . ^^^ Thus , our results indicate that differences in tyrosine phosphorylation of PLC gamma and GAP do not account for the differences in mitogenic activity of the erbB 2 kinase compared with either the EGFR or platelet derived growth factor receptor in NIH 3T3 fibroblasts . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Furthermore , we obtained direct evidence of the constitutive enzymative activity of gp185erbB 2 by demonstrating that the erbB 2 kinase remained active in a chimeric configuration with the extracellular domain of the EGFR , in the absence of any detectable ligand for the EGFR . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
This is substantiated by the facts that EGF and TGF alpha act as autocrine growth factors and then induce the expression of mRNAs for multi growth factors and their receptors ( EGF , TGF alpha , EGFR , ERBB 2 , PDGF ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
An Sp 1 binding site was found , in addition to various sequence motifs common to the promoters of the human neu gene ( erbB 2 ) , the epidermal growth factor receptor gene , and the simian virus 40 enhancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Both EGF and TGF alpha stimulated EGFR phosphorylation , EGF and TGF alpha induced FOS , MYC and ERBB 2 oncogene expression . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
When expression vectors for erbB 2 , which is structurally related to EGFR , or its truncated counterpart , delta NerbB 2 , were introduced into 32D cells , neither was capable of inducing proliferation . ^^^ Thus , EGFR and erbB 2 couple with distinct mitogenic signaling pathways . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Heterodimerization of the erbB 1 and erbB 2 receptors in human breast carcinoma cells : a mechanism for receptor transregulation . ^^^ The erbB 1 and erbB 2 protooncogenes encode homologous membrane receptors that respectively bind epidermal growth factor ( EGF ) and a still incompletely characterized ligand . ^^^ The formation of the latter species is absolutely dependent on the presence of EGF receptor and thus appears to represent a heterodimer of the erbB 1 and erbB 2 receptors . ^^^ In conclusion , heterodimers of erbB 1 and erbB 2 receptors may provide a mechanism for dual transductory functions of growth factors of breast tumor cells . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
When the carboxy terminal domain of erbB 2 was substituted for its analogous region in the epidermal growth factor receptor ( EGFR ) ( EGFR / erbB 2COOH chimera ) , it conferred erbB 2 like properties to the EGFR , including transforming ability in the absence of epidermal growth factor , elevated constitutive autokinase activity in vivo and in vitro , and constitutive ability to phosphorylate phospholipase C gamma . ^^^ Conversely , a chimeric erbB 2 molecule bearing an EGFR carboxy terminal domain ( erbB 2 / EGFRCOOH chimera ) showed reduced transforming and kinase activity with respect to the wild type erbB 2 and was only slightly more efficient than the erbB 2 delta 1050 mutant . ^^^ Thus , we conclude that the carboxy terminal domains of erbB 2 and EGFR exert different regulatory effects on receptor kinase function and biological activity . ^^^ The carboxy terminal domains of erbB 2 and epidermal growth factor receptor exert different regulatory effects on intrinsic receptor tyrosine kinase function and transforming activity . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
To determine whether alterations in oncogenes are associated with tumour progression and metastasis , DNAs from 32 metastatic tumour samples of different sites in 12 autopsy cases of gastric carcinomas were analysed for alterations of ERBB , ERBB 2 , HST 1 , INT 2 and LMYC genes by Southern blot hybridisation . ^^^ In primary tumours , no amplification was detected in early carcinomas , while amplification of ERBB and ERBB 2 genes was detected in one ( 1 . 4 % ) and four ( 5 . 8 % ) out of 69 advanced carcinomas , respectively . ^^^ Regardless of histological type , amplification of ERBB 2 gene was detected in 8 metastatic tumours ( 25 . 0 % ) , out of which three tumours had coamplification of HST 1 and INT 2 genes . ^^^ The incidence of ERBB 2 amplification in metastatic tumours was significantly higher than that in primary tumours . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The neu oncogene , characterized by Weinberg and colleagues , is a transforming gene found in ethylnitrosourea induced rat neuro / glioblastomas ; its human proto oncogene homologue has been termed erbB 2 or HER 2 because of its close homology with the epidermal growth factor receptor ( EGF R ) gene ( c erbB 1 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In contrast , expression of the EGFR related protooncogene HER 2 ( erbB 2 ) was found to be decreased in 11 RCCs and one Wilms ' tumor ; HER 2 gene structure , however , appeared normal in all specimens . ^^^ Aberrant expression of epidermal growth factor receptor and HER 2 ( erbB 2 ) messenger RNAs in human renal cancers . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Of the erbB family genes , erbB 1 ( epidermal growth factor receptor ) was amplified in 10 of 114 tumors and erbB 2 ( HER 2 / neu ) in one of 51 tumors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
A related DNA fragment distinct from the epidermal growth factor receptor and ERBB 2 genes was detected by reduced stringency hybridization of 5 erbB to normal genomic human DNA . ^^^ Characterization of the cloned DNA fragment mapped the region of 5 erbB homology to three exons with closest identity of 64 % and 67 % to a contiguous region within the tyrosine kinase domains of the epidermal growth factor receptor and ERBB 2 proteins , respectively . cDNA cloning revealed a predicted 148 kDa transmembrane polypeptide with structural features identifying it as a member of the ERBB gene family , prompting us to designate the gene as ERBB 3 . ^^^ These findings suggest that increased ERBB 3 expression , as in the case of epidermal growth factor receptor and ERBB 2 , may play a role in some human malignancies . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The epidermal growth factor receptor ( EGF R ) and the erbB 2 proto oncogene product protein are closely related by their structural homology and their shared enzymatic activity as autophosphorylating tyrosine kinases . ^^^ Phosphorylation of erbB 2 does not occur in cells lacking the EGF R ( MDA MB 453 ) . ^^^ This result suggests that the erbB 2 protein is a substrate of the EGF R and indicates the possibility of communication between these two proteins early in the signal transduction process . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The expression of genes which may be involved in the regulation of human mammary epithelial cell growth [ transforming growth factors alpha and beta ] and tumorigenesis [ c myc , erbB 2 , epidermal growth factor receptor ( EGFR ) , Ha ras , pS 2 ] has been compared in similarly cultured normal cell strains and tumor cell lines . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
On the other hand , the erbB 1 / EGF ( epidermal growth factor ) receptor gene and the erbB 2 / neu gene have completely different splicing junctions from those of the above gene group even in the kinase domain , although these genes also have protein kinase activity specific for tyrosine residues and the erbB 1 and 2 genes share splicing sites . ^^^ These results suggest that the genes of the group of six non receptor type kinases and those of the erbB 1 and erbB 2 gene group are descendants evolved by duplication of two distinct ancestor genes and are members of two distinct multi gene families . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Neuregulin can bind directly to erbB 3 and erbB 4 and receptor heterodimerization allows neuregulin dependent activation of erbB 2 ( refs 1 , 2 , 5 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The family currently consists of four closely related members : the epidermal growth factor receptor ( EGF R / erbB 1 ) , erbB 2 , erbB 3 and erbB 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
To study gene amplification in fresh and formalin fixed bladder cancer we used gene specific probes for erbB 2 , EGF r , and 11q13 ( bcl 1 , PRAD 1 ) together with their corresponding centromere probes p17H8 , p7alphaTET and plC11A . ^^^ Amplification was seen in 10 / 140 tumors for erbB 2 , in 5 / 107 tumors for EGF r , and in 15 / 137 tumors for 11q13 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
However , these factors do not directly bind ErbB 2 , and its activation is likely to be mediated via transmodulation by other members of the type I / EGF receptor ( EGFR ) related family of receptor tyrosine kinases . ^^^ An ErbB 2 specific single chain antibody , designed to prevent transit through the endoplasmic reticulum and cell surface localization of ErbB 2 , has been expressed in T47D mammary carcinoma cells , which express all four known members of the EGFR family . ^^^ Thus , our observations demonstrate that ErbB 2 plays a central role in the type I / EGFR related family of receptors and that receptor transmodulation represents a crucial step in growth factor signaling . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
However , the juxtamembrane regions of the epidermal growth factor receptor ( EGFR ) and of the related erbB 2 protein , while important in mitogenic signaling , lack demonstrable tyrosine phosphorylation sites , suggesting that other modalities of receptor transducer interactions exist . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Ecotropic virus , which normally does not infect human cells , when pseudotyped with the modified envelope protein now crosses species to infect human breast cancer cell lines that overexpress HER 2 ( human epidermal growth factor receptor ; also called ERBB 2 ) and HER 4 ( also called ERBB 4 ) , while human breast cancer cell lines expressing low levels of these receptors remain resistant to infection . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Synapse associated expression of an acetylcholine receptor inducing protein , ARIA / heregulin , and its putative receptors , ErbB 2 and ErbB 3 , in developing mammalian muscle . ^^^ ARIA responsive myotubes expressed both erbB 2 and erbB 3 , but little EGFR / erbB1 or erbB 4 . ^^^ In adults , erbB 2 and erbB 3 were localized to the postsynaptic membrane . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 2 and EGFR ( epidermal growth factor receptor ) are expressed in lung adenocarcinomas and associated with a poor prognosis . ^^^ Immunocytochemical analysis revealed erbB 2 and EGFR coexperession as a characteristic feature of most lung adenocarcinomas , and at levels of receptor expression present in bronchial epithelial cells . ^^^ Primary tumours and cell lines expressed EGFR , showing higher basal level phosphotyrosine staining than erbB 2 . ^^^ The growth stimulus that ligand activated erbB 2 and EGFR provides to lung adenocarcinoma cells may establish a background of continued cell proliferation over which other critical transforming events may occur . . ^^^ Expression and activation of erbB 2 and epidermal growth factor receptor in lung adenocarcinomas . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The ddPCR method comprises the co amplification of the single copy gene HBB , the erbB 1 , erbB 2 and erbB 3 oncogenes and the second single copy reference gene SOD 2 under equal reaction conditions . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We have determined the average gene copy numbers ( AGCN ) of the erbB 1 gene , encoding the epidermal growth factor receptor ( EGF R ) , the erbB 2 and the erbB 3 genes in breast , ovarian , oral , and lung cancer tissue by using double differential PCR ( ddPCR ) . ^^^ The ddPCR method comprises the co amplification of the single copy gene HBB , the erbB 1 , erbB 2 and erbB 3 oncogenes and the second single copy reference gene SOD 2 under equal reaction conditions . ^^^ Patients whose breast cancer tissue showed an AGCN for erbB 1 of less than 0 . 4 and greater then 1 . 6 , as expected from the literature , for erbB 2 of greater than 2 . 0 and for erbB 3 of less than 1 . 75 had decreased disease free survival ( DFS ) . ^^^ The quotient of erbB 1 and erbB 2 AGCN was the most significant in multivariate Cox analysis followed by nodal status and progesterone receptor status . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Patterns of p 53 , erbB 2 , and EGF r expression in premalignant lesions of the urinary bladder . ^^^ In this study immunohistochemistry and fluorescence in situ hybridization ( FISH ) were used to examine expression of p 53 , erbB 2 , and epidermal growth factor receptor ( EGF r ) , genomic aberrations , and tumor cell proliferation ( Ki 67 LI ) in normal and dysplastic urothelium . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Some of the Shc associated phosphoproteins ( EGFR , PDGFR , erbB 2 , Met , bcr abl , H 4 ret ) bound both the Shc and Grb 2 SH2 domains in vitro ; others ( p 175 ; p 70 p80 ) only the Shc SH 2 domain and yet others ( p 140 ) only the Grb 2 SH3 domains . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : The aim of the study was not only to detect micrometastatic cells in bone marrow , but also to assess the expression of nuclear proliferation markers ( Ki 67 and p 120 ) and the erbB 2 oncogene ( also known as ERBB 2 ) in these cells and , thus , hopefully improve prognostic precision . ^^^ After primary screening of all marrow samples with MAb CK 2 , representative subgroups of CK18+ samples were selected for co labeling with MAbs either to ErbB ( n = 16 ) , ErbB 2 ( n = 121 ) , Ki 67 ( n = 33 ) , or p 120 ( n = 36 ) protein . ^^^ CONCLUSIONS : The high incidence of ErbB 2 expression on micrometastatic breast cancer cells in the bone marrow suggests that these cells might have been positively selected during early stages of metastasis . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The extent of inhibition correlated with both receptor saturation and affinity of different NDF isoforms , and it was abolished upon overexpression of either EGF receptor or ErbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We studied the expressions of aberrant epidermal growth factor receptor ( EGFR ) gene or erbB 2 , which is highly homologous to EGFR gene , and erbA or estrogen receptor ( ER ) gene , which is highly homologous to erbA , as a preliminary study , to know which oncogene expressions are associated with the development of endometrial cancers . ^^^ Aberrant estrogen receptor gene and erbB 2 expressions . ^^^ ErbB 2 mRNA lacked only extracellular domain ( EX ) , suggesting the lack of downregulation of erbB 2 expression by a ligand , which led to regulated tyrosine kinase activity . ^^^ The behavior of aberrant erbB 2 and ER gene co expressions is considered of similar to that of erbA and erbB co expressions in the chicken introduced by the avian erythroblastosis virus , which leads to the development of erythroblastosis in the chick , and seems to be associated with the development of endometrial cancer . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Evidence is also presented that suggests that an EGF R related protein , ErbB 2 , may be involved in similar Src mediated interactions . ^^^ Overexpression of Src , EGF R , and / or ErbB 2 in breast and colorectal tumor cells suggests the potential that such interactions may contribute to the transformed phenotype of these carcinomas . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Accordingly , cytotoxicity assays were performed on NIH / 3T3 cell lines transfected with EGFR , ErbB 2 , ErbB 3 , or ErbB 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In addition , the mRNA levels of the other members of the epidermal growth factor receptor family , erbB 2 and erbB 3 were also analysed . ^^^ The erbB 2 and erbB 3 were more strongly expressed than the epidermal growth factor receptor in the primary carcinomas . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Four of these genes ( EGF R , IGFI R , CSF 1 R , and PDGF R beta ) were expressed in epithelial cells , whereas four ( erbB 2 , erbB 3 , NGF R , and met ) were not . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The erbB 2 and erbB 3 genes showed no amplification in the tumor specimens investigated in this study . ^^^ Expression of the ERBB 2 protein was present in 54 % ( 20 / 37 ) but immunoreactivity was much weaker than for EGF receptor and in most cases barely detectable by Western analysis and immunocytochemistry . ^^^ Our data from immunohistochemistry indicate that ERBB 2 expression in GBM is closely correlated with EGF receptor levels and is therefore not useful as an independent prognostic parameter . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
When cells containing chimeric receptors composed of the EGF R extracellular domain and intracellular domain of erbB 2 were heat stressed , 125I EGF bound to the receptors , but did not stimulate receptor autophosphorylation . ^^^ Insertion of the erbB 2 tyrosine kinase domain into the EGF R confers heat stress sensitivity to the resultant chimeric receptor . ^^^ Thus , although the EGF R and erbB 2 kinase domains show a high degree of homology , the secondary / tertiary structures of these domains would seem to be stabilized in distinct manners . . ^^^ Differential heat stress stability of epidermal growth factor receptor and erbB 2 receptor tyrosine kinase activities . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Concurrent abnormal expression of ERBB 2 , EGFR , and p 53 genes and clinical disease progression of breast carcinoma . ^^^ We tested this hypothesis in breast carcinoma by immunostaining 89 stage heterogeneous cases for the products of three genes ( p 53 , ERBB 2 , and EGFR ) which are frequently altered in this tumor system . ^^^ Variable relationships were observed between advanced disease stage and immunostaining for individual gene products ( ERBB 2 p = 0 . 05 , EGFR p = 0 . 02 , p 53 p = 0 . 12 , Chi Square test ) . ^^^ In multivariate analysis , individual expression of p 53 outweighed expression of ERBB 2 and EGFR in correlation with outcome . ^^^ Short term recurrence , however , may correlate more closely with abnormal expression of p 53 than with EGFR or ERBB 2 . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Two dimensional gel maps of proteins phosphorylated by the epidermal growth factor receptor ( EGFR ) and erbB 2 kinases were obtained , to investigate the molecular basis of the different biological properties of these two molecules . ^^^ Several proteins were phosphorylated by EGFR or erbB 2 with different stoichiometry . ^^^ In NIH3T3 cells , erbB 2 is 100 fold more transforming than EGFR . ^^^ In the same cell line several proteins were preferentially phosphorylated by erbB 2 , as compared to EGFR . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
To address this question we constructed soluble chimeric proteins between alkaline phosphatase and the extracellular domains of ErbB 2 and either ErbB 3 or ErbB 4 , two newly recognized members of the epidermal growth factor receptor family . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Expression of the erbB 2 family of growth factor receptors and their ligands in breast cancers . ^^^ This group includes the epidermal growth factor receptors , the HER 2 / neu ( erbB 2 ) , HER 3 , and HER 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Amplification and over expression of the EGFR and erbB 2 genes in human esophageal adenocarcinomas . ^^^ We examined 13 cases with esophageal adenocarcinomas and 5 cases with Barrett ' s esophagus for amplification of the EGFR and erbB 2 genes . ^^^ We detected multiple copies of the EGFR gene in 30 . 8 % of the tumors and multiple copies of the erbB 2 gene in 15 . 4 % of the tumors . ^^^ Of the cases with amplification of the erbB 2 gene , co amplification of the EGFR gene was found . ^^^ Immunohistochemical staining of the tissues revealed increased expression of the erbB 2 protein in Barrett ' s mucosa and adenocarcinoma , but no associations between staining intensity and degree of EGFR or erbB 2 gene amplification , histology , or tumor stage were found . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Amplification of the erbb 2 ( Her 2 / NEU ) , erbb 1 ( HER 1 ) and c myc oncogenes is often combined with the deletion of the short arm of chromosome 17 in human carcinoma ] . ^^^ Amplification of oncogenes erbb 2 , erbb 1 , c myc and losses of heterozygosity ( LOH ) at chromosomes 11p ( probe hras 1 ) , 17p ( probe ynz 22 ) and 17q ( probe thh 59 ) were studied in 165 human tumours ( 60 breast , 22 ovary , 40 colorectal , 23 lung , and 20 thyroid carcinomas ) . ^^^ This correlation was mostly due to frequent combinations between erbb 2 amplification and 17p deletions ; the incidence of increased copy number of erbb 1 and c myc oncogenes was not high enough for final conclusions about the association of their alterations with LOH at chromosome 17p . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The inverse regulatory effects of TNF on ERBB 2 and EGFR mRNA levels were evoked by different signaling pathways of p 55 TNF receptors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Several of the newer biologic markers of breast cancer may provide very specific treatment information . erbB 2 may predict for improved response to doxorubicin , rather than CMF . hsp 27 may predict for failure of doxorubicin . pS 2 or EGFR may provide supplemental information predicting response to hormonal therapy . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
A related DNA fragment distinct from epidermal growth factor receptor and erbB 2 genes was detected by reduced stringency hybridization of 5 erbB to normal genomic human DNA . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Since ST 3 mRNA expression was independent of the EGFR , ER and erbB 2 protein expression , ST 3 may be a new potent prognostic guide for breast carcinomas , which can detect highly malignant subpopulations . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Cluster analysis revealed the markers fell into three independent groups : ( 1 ) G actin and EGFR ; ( 2 ) ploidy , cytology , and p 185 ( HER 2 / neu oncoprotein ) ( ERBB 2 ) ; and ( 3 ) p 300 , a low grade tumor antigen . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 1 , erbB 2 and abl oncogenes encoding tyrosine kinases , ras oncogenes encoding GTP binding proteins and myc oncogenes whose functions are not well understood are some examples . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The predicted human erbB 3 gene product is closely related to epidermal growth factor receptor ( EGFR ) and erbB 2 , which have been implicated as oncogenes in model systems and human neoplasia . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The expression of mRNAs for epidermal growth factor ( EGF ) , transforming growth factor alpha ( TGF alpha ) , EGFR , platelet derived growth factor ( PDGF ) A and B chain , PDGF receptor ( PDGFR ) , transforming growth factor beta ( TGF beta ) , erbB 2 and estrogen receptor ( ER ) genes was first examined in 6 human esophageal carcinoma cell lines , 6 xenoplanted and 15 surgically resected esophageal carcinomas . ^^^ TGF alpha increased the accumulation of mRNAs for EGF , TGF alpha , EGFR , PDGF A and B chain and the erbB 2 gene . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The frequency of expression and localization of cripto 1 ( CR 1 ) , amphiregulin ( AR ) , transforming growth factor alpha ( TGF alpha ) , epidermal growth factor receptor ( EGFR ) and erbB 2 were examined by immunohistochemistry in 45 carcinomas and adjacent non involved normal colon mucosa . ^^^ Thirty ( 66 . 7 % ) , 24 ( 53 . 3 % ) , 23 ( 51 . 1 % ) , 23 ( 51 . 1 % ) and 13 ( 28 . 9 % ) of the 45 carcinomas showed positive staining for CR 1 , AR , TGF alpha , EGFR and erbB 2 , respectively , whereas 7 ( 15 . 5 % ) , 17 ( 37 . 7 % ) , 15 ( 33 . 3 % ) , 20 ( 44 . 4 % ) and 0 ( 0 % ) of the corresponding non involved normal mucosa specimens were reactive . ^^^ Among 13 carcinomas with lymph node involvement , 10 ( 76 . 9 % ) , 8 ( 61 . 5 % ) , 10 ( 76 . 9 % ) , 8 ( 61 . 5 % ) and 7 ( 53 . 8 % ) exhibited positive staining for CR 1 , AR , TGF alpha , EGFR and erbB 2 , respectively . ^^^ These data suggest that AR and TGF alpha may play an important role in the development of colorectal carcinomas through an autocrine mechanism involving EGFR , and demonstrate that TGF alpha and erbB 2 may be more reliable indicators of metastasis or prognosis than CR 1 , AR or EGFR in human colon cancers . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Neu differentiation factor activation of ErbB 3 and ErbB 4 is cell specific and displays a differential requirement for ErbB 2 . ^^^ NDF induced phosphorylation of ErbB 2 and ErbB 3 was found in the breast epithelial cell line MCF10A , the breast tumor cell lines T47D and MCF 7 , and the ovarian tumor cell line OVCAR 3 . ^^^ Blocking cell surface expression of ErbB 2 by intracellular expression of a single chain antibody revealed that in these two cell lines , ErbB 2 significantly enhanced phosphorylation of ErbB 4 . ^^^ Efficient NDF induced phosphorylation of ErbB 3 was strictly ErbB 2 dependent in the breast tumor cell lines T47D and MCF 7 , while it was largely ErbB 2 independent in MCF10A and OVCAR 3 cells . ^^^ Consequently , NDF stimulated intracellular signaling and induction of a biological response displayed a cell specific requirement for ErbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
WIN 61651 , which is competitive with ATP , demonstrates selectivity for the lymphoid restricted tyrosine kinase p56lck over serine / threonine kinases , such as protein kinase C and protein kinase A , and over some other tyrosine kinases , including erbB 2 , epidermal growth factor receptor , and insulin receptor ; however , it is equipotent for inhibition of p56lck and the platelet derived growth factor receptor tyrosine kinases . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Concomitant overexpression of the EGFR and erbB 2 genes in renal cell carcinoma ( RCC ) is correlated with dedifferentiation and metastasis . ^^^ We investigated 34 renal cell carcinomas for gene amplification and expression of the EGFR and erbB 2 genes at the mRNA and protein level and their relationship to pathological and clinical parameters . ^^^ However , the role of erbB 2 in these processes remains unknown . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Four transmembrane tyrosine kinases constitute the ErbB receptor family : the epidermal growth factor ( EGF ) receptor , ErbB 2 , ErbB 3 , and ErbB 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
A bivalent single chain antibody toxin specific for ErbB 2 and the EGF receptor . ^^^ ErbB 2 and EGF receptors are often co expressed in human tumors and have been shown to synergize in the transformation of cells in experimental model systems . ^^^ Transactivation of ErbB 2 can occur via ligand induced heterodimerization with EGF receptor or other members of the ErbB family of receptor tyrosine kinases . ^^^ We have previously described the potent anti tumoral activity of the monospecific single chain antibody toxins scFv ( FRP 5 ) ETA and scFv ( 225 ) ETA binding to , respectively , ErbB 2 and the EGF receptor . ^^^ The fusion protein consists of 2 scFv domains specific for ErbB 2 and the EGF receptor linked to a modified Pseudomonas exotoxin A . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In order to explore the signal transduction pathways potentially activated by NDF , we examined expression of the receptors erbB 2 , erbB 3 and erbB 4 in mammary epithelial cells established from an NDF induced tumor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In contrast , all the EGF related factors except amphiregulin were able to induce tyrosine phosphorylation of ErbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
EGF markedly increased ErbB 2 tyrosine phosphorylation in wild type EGFR cells . ^^^ In Delta 973 EGFR cells , ErbB 2 was tyrosine phosphorylated in the basal state and EGFR stimulated further phosphorylation of ErbB 2 . ^^^ In addition to ErbB 2 , additional proteins were tyrosine phosphorylated in Delta 973 EGFR cells , mostly in the molecular mass range of 120 170 kDa . ^^^ Taken together with our findings indicating coupling of ErbB 2 to Shc , these data suggest the importance of an alternative signaling pathway in Delta 973 EGFR cells mediated by the formation of heterodimeric structures between the truncated EGFR and ErbB 2 , followed by coupling through Shc to Grb2 . ^^^ Involvement of ErbB 2 in the signaling pathway leading to cell cycle progression from a truncated epidermal growth factor receptor lacking the C terminal autophosphorylation sites . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
SUM 52PE cells are epidermal growth factor receptor negative but express single copy levels of erbB 2 protein . ^^^ Southern blot analysis indicates that the erbB 2 gene is not amplified in these cells . ^^^ Immunoprecipitation , using antibodies to erbB 2 or erbB 3 , coupled to phosphotyrosine Western blot analysis indicates that both erbB 2 and erbB 3 are constitutively tyrosine phosphorylated in proliferating SUM 52PE cells . ^^^ Conditioned medium obtained from SUM 52PE cells does not induce tyrosine phosphorylation of p185erbB 2 in a sensitive indicator cell line , suggesting that an erbB 2 activating factor is not secreted by these cells . ^^^ Thus , SUM 52PE cells synthesize a membrane bound form of NDF / HRG that may activate erbB 2 and erbB 3 via a juxtacrine mechanism . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The group of subtype 1 transmembrane tyrosine kinases includes the epidermal growth factor ( EGF ) receptor ( ErbB 1 ) , an orphan receptor ( ErbB 2 ) , and two receptors for the Neu differentiation factor ( NDF / heregulin ) , namely : ErbB 3 and ErbB 4 . ^^^ By using the generated mAbs , we found that the major NDF receptor on mammary epithelial cells is a heterodimer of ErbB 3 with ErbB 2 , whereas an ErbB 1 / ErbB 2 heterodimer , or an ErbB 1 homodimer , is the predominant species that binds EGF . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The ErbB family includes two receptors , ErbB 1 and ErbB 3 , that respectively bind to epidermal growth factor and Neu differentiation factor , and an orphan receptor , ErbB 2 . ^^^ Unlike ErbB 1 and ErbB 2 , the intrinsic tyrosine kinase of ErbB 3 is catalytically impaired . ^^^ By using interleukin 3 dependent cells that ectopically express the three ErbB proteins or their combinations , we found that ErbB 3 is devoid of any biological activity but both ErbB 1 and ErbB 2 can reconstitute its extremely potent mitogenic activity . ^^^ Inter receptor interactions enable graded proliferative and survival signals : heterodimers are more potent than homodimers , and ErbB 3 containing complexes , especially the ErbB 2 / ErbB 3 heterodimer , are more active than ErbB 1 complexes . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Previously we reported that neu differentiation factor ( NDF ) / heregulin ( HRG ) elevates tyrosine phosphorylation of its receptors erbB 3 , erbB 4 , and erbB 2 ( through heterodimer formation ) . ^^^ We also showed that both NDF / HRG and antibodies to erbB 2 can arrest growth and induce differentiation in breast cancer cells . ^^^ We show that NDF / HRG and antibodies to erbB 2 receptors up regulate expression of p 53 by stabilizing the protein . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
TPA did not induce the degradation of related receptors ( ErbB 1 , ErbB 2 , and ErbB 3 ) in the EGF receptor family . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Growth regulation of human breast and ovarian tumor cells by heregulin : Evidence for the requirement of ErbB 2 as a critical component in mediating heregulin responsiveness . ^^^ In biologically relevant systems , interaction of HRG with ErbB 3 or ErbB 4 results in the transactivation of ErbB 2 . ^^^ In this report , we show that ErbB 2 is a critical component in mediating HRG responsiveness in a panel of human breast and ovarian tumor cell lines . ^^^ HRG binding studies were performed with a panel of breast and ovarian tumor cell lines expressing a range of levels of ErbB 2 . ^^^ The biological responses to HRG were also compared to EGF and to the growth inhibitory anti ErbB 2 antibody , 4D5 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The ErbB family of transmembrane tyrosine kinases includes the receptor for EGF ( ErbB 1 ) , two receptors for NDF / heregulin ( ErbB 3 and ErbB 4 ) and an orphan receptor ( ErbB 2 ) . ^^^ Likewise , activation of a chimeric ligand stimulatable ErbB 2 by a heterologous ligand was ineffective . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Overexpression of the epidermal growth factor receptor ( EGFR ) and ErbB 2 has been observed in a variety of human tumours , making these receptors promising targets for directed tumour therapy . ^^^ Since many tumour cells express both ErbB 2 and EGFR and these receptors synergise in cellular transformation , therapeutic reagents simultaneously binding to ErbB 2 and EGFR might offer advantages for tumour therapy . ^^^ We have previously described the potent anti tumoral activity of a bispecific antibody toxin that contains ErbB 2 and EGFR specific single chain Fv ( scFv ) domains . ^^^ The fusion protein consists of the antigen binding domain of the ErbB 2 specific MAb , FRP 5 , and the natural EGFR ligand , TGF alpha , inserted at different positions in truncated Pseudomonas exotoxin A . ^^^ ScFv ( FRP 5 ) TGF alpha ETA protein displayed binding to EGFR and ErbB 2 , thereby inducing activation of the receptors , which was dependent on the cellular context and the level of EGFR and ErbB 2 expression . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We show that erbB 2 , erbB 3 and erbB 4 are concentrated at synaptic sites in adult skeletal muscle . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Amplification and / or overexpression of the oncogenes epidermal growth factor receptor and erbB 2 are associated with later stage disease . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Both groups bind to the catalytically impaired receptor tyrosine kinase ErbB 3 , whose mitogenic stimulation by NDF requires transactivation by other ErbB proteins , either ErbB 1 or ErbB 2 . ^^^ By expressing each pair of receptors in interleukin 3 dependent myeloid cells , we found that both isoforms induced mitogenic signals in cells co expressing the combination of ErbB 3 with ErbB 2 . ^^^ These results imply that NDF isoforms differ in their ability to induce receptor heterodimers ; whereas both types of isoforms signal through ErbB 3 / ErbB 2 heterodimers , only beta isoforms are able to stabilize ErbB 3 / ErbB 1 heterodimers . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In order to examine the effects of scFv R1R and scFv 5R on the long term growth of tumor cells overexpressing either EGFR or ErbB 2 , retroviruses encoding the two scFvs were used to infect various human tumor cell lines . ^^^ However , in some cases expression of both scFvs was incompatible with long term cell growth suggesting that heterodimers of ErbB 2 and EGFR are essential for the growth of some human tumor cell lines . . ^^^ We have recently shown that scFv 5R directed to ErbB 2 , another member of the ErbB family , blocks the anchorage independent growth of ErbB 2 transformed cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The erbB 2 proto oncogene encodes a transmembrane protein ( p 185 ) that is a tyrosine kinase sharing high homology with the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We report here on the expression in mammalian cells of cDNAs encoding scFv 225 and scFv FRP 5 directed against the extracellular domain of , respectively , human EGFR and human ErbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
EGF R , ErbB 3 , and ErbB 4 were not detected in the CHK immunoprecipitates or in the precipitates of the GST SH 2 fusion proteins of CHK , suggesting that the association of CHK with ErbB 2 upon heregulin stimulation is receptor specific ( ErbB 2 ) and ligand specific ( heregulin ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Expression of neuregulins and their putative receptors , ErbB 2 and ErbB 3 , is induced during Wallerian degeneration . ^^^ Of the four known erbB kinases , Schwann cells express both erbB 2 and erbB 3 receptors over the entire interval studied . ^^^ Expression of erbB 2 and erbB 3 is coordinately induced in response to axotomy , indicating that Schwann cell responses to NRGs may be modulated by changes in receptor density . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The EGF family includes EGF , transforming growth factor alpha , heparin binding EGF , amphiregulin , beta cellulin , epiregulin , and heregulins , whereas the receptor family ( the erbB genes ) consists of erbB 1 ( EGF receptor , EGF R ) , erbB 2 , erbB 3 , and erbB 4 . ^^^ Differential expression of the erbB 2 gene in the periimplantation mouse uterus : potential mediator of signaling by epidermal growth factor like growth factors . ^^^ Thus , we examined the expression of the erbB 2 gene in the mouse uterus during the periimplantation period ( days 1 8 of pregnancy ) and after 17 beta estradiol and / or progesterone stimulation . ^^^ Northern blot hybridization detected two transcripts ( approximately 4 . 0 and 5 . 0 kb ) of erbB 2 messenger RNA ( mRNA ) in day 1 8 uterine polyadenylated RNA samples . ^^^ In situ hybridization experiments showed unique uterine cell specific erbB 2 mRNA distribution . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Here we show additional evidence for the activation of epidermal growth factor receptor ( EGFR ) , and we show activation of 5 ErbB , ErbB 2 and platelet derived growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
After DNA extraction , the ERBB 1 , ERBB 2 and ERBB 3 copy number in tumour samples was estimated with the polymerase chain reaction ( PCR ) method . ^^^ None of the 59 cases presented amplification of ERBB 2 and ERBB 3 oncogenes . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The Grb 7 protein was recently identified as a substrate of the epidermal growth factor receptor and related Her2 / erbB 2 receptor linked tyrosine kinase activity . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
RESULTS : No significant correlation between common prognostic parameters and erbB 2 amplification was found . ^^^ Patients whose OSCC tissue showed an average gene copy number for erbB 2 of greater than 1 . 2 , for erbB 3 below 0 . 11 , and a ratio of erbB 1 and erbB 2 below 0 . 31 had a statistically significant decrease in disease free survival . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We report the use of structure based drug design to create a selective erbB 1 ( a . k . a . epidermal growth factor receptor ) and erbB 2 ( a . k . a . neu / her2 growth factor receptor ) tyrosine kinase inhibitor . ^^^ This information , combined with homology modeling of the erbB 1 and erbB 2 tyrosine kinase catalytic domains , has led to the identification of Cys 797 of erbB 1 and Cys 805 of erbB 2 , which are structurally equivalent to Glu 127 in the cAMP dependant Ser / Thr kinase as potential target residues . ^^^ Using molecular modeling , it was predicted that the Cys side chains in erbB 1 and erbB 2 performed an analogous role , and it was postulated that the replacement of the 2 ' OH of adenosine with a thiol might allow for a covalent bond to form . ^^^ Since only erbB 1 and erbB 2 have a Cys at this position , the inhibitor should be selective . ^^^ This model was subsequently tested experimentally by chemical synthesis of 2 ' thioadenosine and assayed against the full length erbB 1 receptor and the catalytic domains of erbB 2 , insulin receptor , beta PDGF receptor , and the FGF receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The erbB 2 oncogene and chemotherapy : a mini review . ^^^ The erbB 2 gene , also known as Her 2 / neu , is an oncogene that encodes a transmembrane glycoprotein receptor . ^^^ When overexpressed erbB 2 is an indicator of poor prognosis in a number of cancers . ^^^ Recent studies show that erbB 2 expression plays a role in the prediction of responsiveness to adjuvant treatment : tumors that had an overexpression of the oncogene were less responsive to treatment than those with a normal amount . ^^^ Some studies on this oncogene have examined the production of anti erbB 2 monoclonal antibodies and evaluated the combined effect of monoclonal antibody and chemotherapeutics . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Included in this overview are epidermal growth factor receptor and its ligands , erbB 2 , fibroblast growth factors , insulin like growth factor , the transferrin receptor , and transforming growth factor beta . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The epidermal growth factor receptor ( EGF R ) is known to transmodulate the activity and level of the erbB 2 / neu protein in several epithelial cell lines . ^^^ We therefore determined which structural features of the EGF R were important in transmodulating erbB 2 . ^^^ We found that the addition of EGF to nontransformed epithelial cells resulted in down regulation of erbB 2 with the same kinetics and similar extent as the EGF R . ^^^ By using cells expressing a series of EGF R modified by site directed mutagenesis , we found that EGF R tyrosine kinase activity was not necessary for down regulation of erbB 2 , but receptor sequences between 899 and 958 in the EGF R were required . ^^^ Again , phosphorylation of erbB 2 following EGF addition did not require the intrinsic tyrosine kinase activity of the EGF R , but did require sequences between 899 and 958 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 2 , the preferred heterodimerization partner of all ErbB receptors , is a mediator of lateral signaling . ^^^ Down regulation of cell surface ErbB 1 or ErbB 2 by intracellular expression of specific antibodies has allowed us to delineate the role of these receptors during signaling elicited by : EGF and heparin binding EGF ( HB EGF ) , ligands of ErbB 1 ; betacellulin ( BTC ) , a ligand of ErbB 1 and ErbB 4 ; and neu differentiation factor ( NDF ) , a ligand of ErbB 3 and ErbB 4 . ^^^ Ligand induced ErbB receptor heterodimerization follows a strict hierarchy and ErbB 2 is the preferred heterodimerization partner of all ErbB proteins . ^^^ NDF activated ErbB 3 or ErbB 4 heterodimerize with ErbB 1 only when no ErbB 2 is available . ^^^ If all ErbB receptors are present , NDF receptors preferentially dimerize with ErbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Furthermore , an increase in erbB 2 : EGFr heterodimer formation was also induced by EGF . ^^^ In contrast to the results with erbB 2 , EGF did not induce tyrosine phosphorylation , the degradation of erbB 3 , or erbB 3 : EGFr heterodimer formation in cultured keratinocytes . ^^^ Concomittantly , erbB 2 : EGFr heterodimer formation and c src kinase activity were also elevated in TPA treated epidermis . ^^^ Collectively , the current data suggest that the activation of erbB 2 in phorbol ester treated skin can be explained solely by a mechanism involving elevation of EGFr ligands and activation of the EGFr . ^^^ In addition , activation of c src may be an important downstream effector in mouse keratinocytes both in vivo and in vitro , following activation of the EGFr , erbB 2 , or both . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Several growth factors ( TGF alpha , HGF ) and their receptors ( EGFR , MET , ERBB 2 ) were expressed in the primitive IBS cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Competitive differential polymerase chain reaction for gene dosage estimation of erbB 1 ( egfr ) , erbB 2 , and erbB 3 oncogenes . ^^^ Therefore , we describe a quantitative PCR method for the estimation of AGCN in the oncogenes erbB 1 ( egfr ) , erbB 2 , and erbB 3 . ^^^ Using this method , we confirmed egfr and erbB 2 amplification in cancer cell lines and tumor tissue , and we also detected erbB 3 amplifications . ^^^ Increases in the average gene copy number ( AGCN ) of the erbB oncogenes , especially the erbB 2 gene , have been found in a variety of human cancers . ^^^ Furthermore , gene dosage decreases were detectable , e . g . , an erbB 2 hemizygosity in MCF 7 cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Through their interaction with the ErbB family of receptors ( ErbB 2 , ErbB 3 and ErbB 4 ) , neuregulins help to regulate cell growth and differentiation in many tissues . ^^^ Recombinant neuregulin 2beta induces the tyrosine phosphorylation of ErbB 2 , ErbB 3 and ErbB 4 in cell lines expressing all of these ErbB family receptors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We have isolated four splice variants , two each from human and mouse , and have shown that they are capable of inducing tyrosine phosphorylation of erbB 3 , erbB 4 , and erbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Further complexity is added due to the existence of an oncogenic receptor that enhances and stabilizes dimerization but has no ligand ( ErbB 2 ) , and a receptor that can recruit novel SH 2 containing proteins , but is itself devoid of kinase activity ( ErbB 3 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In SKBR 3 cells , the quinazolines induced the formation of inactive EGFR / ErbB 2 heterodimers , potentially sequestering ErbB 2 from interacting with other coreceptors of the ErbB family . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In a similar fashion , EGF receptor ( EGFR ) agonists induce heterodimers of EGFR and ErbB 2 . ^^^ None of the EGFR agonists tested ( EGF , beta cellulin , or heparin binding EGF ) inhibited growth of ErbB 2 overexpressing cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The expression of genes involved in mitotic signal pathway ( EGF , TGF alpha , EGF R , erbB 2 , erbB 3 , c myc and c H ras ) was determined immunocytochemically . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Comparison of phorbol ester and sphingomyelinase induced phosphorylation of ErbB 2 and ErbB 3 . ^^^ Chem . 272 , 31172 31181 ) , we demonstrated that phorbol 12 myristate 13 acetate ( PMA ) treatment of Fao cells induces tyrosine phosphorylation of several proteins including ErbB 2 and ErbB 3 . ^^^ In the present study we show that sphingomyelinase also results in the enhanced tyrosine phosphorylation of ErbB 2 and ErbB 3 in these cells . ^^^ Prolonged insulin treatment resulted in decreased expression of both ErbB 2 and ErbB 3 . ^^^ Insulin also appears to negatively regulate the protein tyrosine kinase responsible for phosphorylating ErbB 2 in PMA stimulated cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 3 is an epidermal growth factor receptor related type 1 tyrosine kinase receptor capable , in conjunction with ErbB 2 or epidermal growth factor receptor , of transmitting proliferative and differentiative signals in a variety of cell types . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The epidermal growth factor receptor ( EGFR ) is activated by a variety of ligands including EGF and transforming growth factor alpha ( TGFalpha ) , whereas no ligand for the homologous ErbB 2 oncoprotein has yet been identified . ^^^ Here we use both an ErbB 2 phosphoantibody ( aPY 1222 ) and an activation specific EGFR antibody to show that low concentrations of EGF induce more efficient tyrosine phosphorylation of ErbB 2 in A 431 cells than does equimolar TGFalpha , while EGFR is more potently activated by TGFalpha . ^^^ Co precipitation studies confirm that heterodimerization of activated EGFR and transphosphorylated ErbB 2 is readily induced by EGF but not TGFalpha . ^^^ EGFR downregulation is also more efficiently induced by EGF , suggesting that ligand dependent modification of ErbB 2 may be required to terminate EGFR signalling in cells expressing both receptor types . ^^^ These findings indicate that EGF and TGFalpha differ in their abilities to induce tyrosine phosphorylation and heterodimerization of ErbB 2 , and raise the possibility that ErbB 2 exerts its oncogenic effect in part by impairing TGFalpha dependent EGFR downregulation . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
LNCaP stimulated with NDF demonstrated crosstalk between ErbB 3 and ErbB 2 which did not involve ErbB 1 . ^^^ The activation of mHOG by ErbB 2 or ErbB 3 has not been reported , and may contribute to the unusual phenotype . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Two receptor tyrosine kinases , ErB 3 and ErbB 4 , mediate signaling by Neu differentiation factors ( NDFs , also called neuregulins ) , while ErbB 1 and ErbB 2 serve as co receptors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Chemical cross linking experiments showed that [ 125I ] epiregulin directly bound to each of EGFR and ErbB 4 but not to ErbB 2 and ErbB 3 . ^^^ Epiregulin binds to epidermal growth factor receptor and ErbB 4 and induces tyrosine phosphorylation of epidermal growth factor receptor , ErbB 2 , ErbB 3 and ErbB 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The ErbB 2 system , also called HER 2 or neu , is analogous to the epidermal growth factor receptor system ( EGF R , ErbB 1 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The role of ErbB 2 tyrosine kinase receptor in cellular intrinsic chemoresistance : mechanisms and implications . ^^^ Of particular interest is the intrinsic drug resistance associated with overexpression of the erbB 2 receptor . ^^^ In general , tumor cells overexpressing erbB 2 are intrinsically resistant to DNA damaging agents such as cisplatin . ^^^ While the molecular mechanisms by which erbB 2 induces drug resistance are not yet established , there is evidence that this may be a consequence of altered cell cycle checkpoint and DNA repair mechanisms and dysregulation of apoptotic pathway ( s ) . ^^^ Blockade of erbB 2 signaling using erbB 2 antagonists , dominant negative mutants , or chemical inhibitors of erbB 2 tyrosine kinase activity induces cell cycle arrest , inhibits DNA repair , and ( or ) promotes apoptosis . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
HRG also triggers association of epidermal growth factor receptors ( EGFR ) with a kinase inactive ErbB 2 subset while reducing EGFR association with active ErbB 2 . ^^^ Similarly , EGF treatment of A 431 cells induces concomitant hetero oligomerization of active ErbB 2 with inactive EGFR , of active EGFR with inactive ErbB 2 , and of inactive ErbB 2 with kinase defective ErbB 3 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB / epidermal growth factor receptor and ErbB 2 are receptors that may be important in breast tumour development and normal mammary growth control . ^^^ Overactive ErbB 2 causes local development of alveoli , suggesting that it may be involved in normal alveolus development . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The type 1 family of growth factor receptors consists of the epidermal growth factor receptor ( EGFR ) , and ErbB 2 , ErbB 3 and ErbB 4 . ^^^ Six ligands are known to bind directly to EGFR , none ( at present ) to ErbB 2 , and a family of ligands collectively called the neuregulins bind to both ErbB 3 and ErbB 4 . ^^^ Overexpression of EGFR , ErbB 2 and ErbB 3 has been found commonly in solid human tumours . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Co expression of erbB 2 with erbB 3 point mutants was used to map Grb 7 binding sites . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We have determined the expression of transforming growth factor alpha ( TGF alpha ) , amphiregulin ( AR ) , CRIPTO , the epidermal growth factor receptor ( EGFR ) , erbB 2 , erbB 3 , and tumor angiogenesis in a series of 195 patients with stage 1 IIIA non small cell lung cancer ( NSCLC ) treated with radical surgery to define their usefulness as prognostic indicators of survival . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The ErbB 2 / HER2 oncogenic receptor of adenocarcinomas : from orphanhood to multiple stromal ligands . ^^^ Extensive clinical and biochemical evidence implicates ErbB 2 , a transmembrane tyrosine kinase related to growth factor receptors , in the development , metastasis , and resistance to therapy of multiple , common human carcinomas . ^^^ Previous attempts to uncover an ErbB 2 specific ligand led to isolation of the neuregulin ( NRG ) family , but these ligands , like all other growth factors with an EGF like motif , only indirectly active ErbB 2 . ^^^ On the other hand , biochemical and genetic evidence suggest a non autonomous function of ErbB 2 in an interactive ErbB signaling network . ^^^ By stabilizing heterodimers with other ErbB proteins , ErbB 2 prolongs and enhances signal transduction by a large group of stroma derived growth factors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The oncogenic ErbB 2 / ErbB 3 heterodimer is a surrogate receptor of the epidermal growth factor and betacellulin . ^^^ The fourth member of the ErbB family , ErbB 2 , acts as the preferred heterodimeric partner of ligand occupied complexes of the three other ErbB proteins . ^^^ The functional receptor was identified as a heterodimer between ErbB 3 and ErbB 2 , a previously identified oncogenic complex . ^^^ When singly expressed , neither ErbB 3 nor ErbB 2 can mediate signaling by EGF . ^^^ In addition , when co expressed , blocking either receptor by using site specific antibodies inhibited EGF and betacellulin activities , indicating strict cooperativity between ErbB 3 and ErbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Activation of ErbB 4 by the bifunctional epidermal growth factor family hormone epiregulin is regulated by ErbB 2 . ^^^ Finally , ErbB 2 , which is not activated by EPR when expressed on its own , increases the sensitivity of ErbB 4 for activation by EPR . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The erbB 2 proto oncogene belongs to a receptor tyrosine kinase family that includes the epidermal growth factor receptor , erbB 2 , erbB 3 , and erbB 4 . erbB 2 is expressed in basal cells of the squamous epithelia and the outer root sheath of the hair follicles , but its function in epidermal development has not been well studied . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Members of the type 1 receptor tyrosine kinase family , including epidermal growth factor ( EGF ) receptor ( EGFR ) and ErbB 2 / neu , are often overexpressed in various human cancer cells , including breast . ^^^ Cells that do not express ErbB 4 but express ErbB 3 receptor , together with the ErbB 2 or EGFR , exhibited moderate sensitivity to HRG PE toxins . ^^^ HRG PE toxins have little or no activity against cells expressing EGFR , ErbB 2 , or ErbB 3 alone . ^^^ We conclude that there is therapeutic potential of HRG PE toxins in the therapy of cancers overexpressing the ErbB 4 or ErbB 2 plus ErbB 3 receptors . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Although HRG can bind to ErbB 3 and ErbB 4 homodimers , the highest affinity and most intracellularly active receptor complexes are hetero oligomers containing ErbB 2 . ^^^ The optimized variants stimulated ErbB 2 phophorylation on MCF 7 cells at levels similar to wild type . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In this study , we show that agrin induced induction of AChR epsilon subunit gene transcription is inhibited in cultured myotubes overexpressing an inactive mutant of the ErbB 2 receptor , demonstrating involvement of the NRG / ErbB pathway in agrin induced AChR expression . ^^^ Furthermore , salt extracts from the surface of cultured myotubes induce tyrosine phosphorylation of ErbB 2 receptors , indicating that muscle cells express biological NRG like activity on their surface . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The levels of EGFR were similar in non tumorigenic E 2 and tumorigenic E6T cells but higher in E2alpha and E6TA cells , and ErbB 2 were greatly overexpressed in an E2alpha clone . ^^^ In vitro , ErbB 2 co immunoprecipitated with EGFR in lysates of unstimulated E6T and E2alpha TGF alpha producing cells , indicating that the lower TGF alpha levels were sufficient to induce in vitro heterodimerization . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Amplification and / or overexpression of the ERBB genes are a feature of many cancer types , and overexpression of erbB 2 correlates with poor prognosis in epithelial ovarian cancer . ^^^ Ten of 12 tumors expressed erbB 4 at moderate to high levels in > 50 % of cancer cells , whereas erbB 2 ( 6 of 12 ) and erbB 3 ( 2 of 12 ) were expressed less frequently . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
METHODS : A total of 17 serous cystadenocarcinomas were analyzed for epidermal growth factor receptor ( EGF R or ErbB 1 ) and ErbB 2 , ErbB 3 , and ErbB 4 receptor expression by Western blot analysis . ^^^ RESULTS : All 17 tumors expressed detectable levels of EGF R , ErbB 2 , and ErbB 3 , but ErbB 4 expression was not detected . ^^^ EGF R levels correlated with ErbB 2 ( r = . 70 , P < . 01 ) and ErbB 3 ( r = . 52 , P < . 05 ) levels . ^^^ EGF R levels correlated with ErbB 2 ( r = . 70 , P < . 01 ) and ErbB 3 ( r = . 52 , P < . 05 ) levels . ^^^ The highest correlation was obtained between the levels of ErbB 2 and ErbB 3 ( r = 0 . 81 , P < . 001 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 2 expression increases the spectrum and potency of ligand mediated signal transduction through ErbB 4 . ^^^ E4 ) or with ErbB 2 ( 32D . ^^^ Although coexpression of ErbB 2 with ErbB 4 in 32D . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Transient cotransfection of erbB 2 mutant and chimeric molecules demonstrated that the cytoplasmic domain of erbB 2 , or the homologous cytoplasmic domain of the epidermal growth factor receptor , is required for apoptosis induction . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Co expression of ErbB 2 , a developmentally important co receptor whose expression is frequently elevated in human cancers , specifically potentiated EGF signaling to the level achieved by TGFalpha , an effect that was partially mimicked by ErbB 3 . ^^^ Analysis of the mechanism underlying this trans potentiation implied that EGF driven homodimers of ErbB 1 are destined for intracellular degradation , whereas the corresponding heterodimers with ErbB 2 or with ErbB 3 , dissociate in the early endosome . ^^^ In addition , the ability of ErbB 2 to shunt ligand activated receptors to recycling may explain , in part , its oncogenic potential . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
This superactivation must be a result of heterodimer formation between EGFR and ErbB 2 , since EGF is not a ligand for ErbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The ErbB 2 and ErbB 3 receptors and their ligand , neuregulin 1 , are essential for development of the sympathetic nervous system . ^^^ Here , we report a novel phenotype in mice with targeted mutations in the erbB 2 , erbB 3 , or neuregulin 1 genes . ^^^ Thus , neuregulin 1 , erbB 2 , and erbB 3 are required for the formation of the sympathetic nervous system ; the block in development observed in mutant mice is caused by a lack of neural crest precursor cells in the anlage of the primary sympathetic ganglion chain . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The ErbB family of receptors , which include the epidermal growth factor receptor ( EGFR ) , ErbB 2 , ErbB 3 , and ErbB 4 mediate the actions of a family of bioactive polypeptides . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
When this protein was immunoprecipitated with antibody against epidermal growth factor receptors ErbB 1 , ErbB 2 , ErbB 3 or ErbB 4 , it was immunoprecipitated only by the anti ErbB 1 antibody . ^^^ Betacellulin induced the tyrosine phosphorylation of ErbB 1 , ErbB 2 and ErbB 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Thus , in the virgin gland , ERBB 1 and ERBB 2 were colocalized to all major cell types during ductal morphogenesis but differentially localized in the mature gland . ^^^ Thus , exogenous EGF induced stage dependent transphosphorylation of ERBB 2 4 as well as ERBB 1 , whereas endogenous phosphorylation of all four receptors peaked in late pregnancy and lactation . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Cultured HPDE cells express low levels of epidermal growth factor receptor ( EGFR ) , erbB 2 , transforming growth factor ( TGF ) alpha , Met / hepatocyte growth factor receptor ( HGFR ) , vascular endothelial growth factor ( VEGF ) , and keratinocyte growth factor ( KGF ) . ^^^ In comparison , pancreatic carcinoma cell lines commonly demonstrated overexpression of EGFR , erbB 2 , TGF alpha , Met / HGFR , VEGF , and KGF , but they consistently showed marked down regulation of amphiregulin mRNA expression . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Expression of receptors for neuregulins , ErbB 2 , ErbB 3 and ErbB 4 , in developing mouse cerebellum . ^^^ We have examined the expression of ErbB 2 , ErbB 3 and ErbB 4 in developing mouse cerebellum . ^^^ ErbB 2 , ErbB 3 and ErbB 4 were all expressed in granule cells during cerebellar development . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Formation of a high affinity heregulin binding site using the soluble extracellular domains of ErbB 2 with ErbB 3 or ErbB 4 . ^^^ ErbB 2 functions as a shared signal transducing component for other ErbB receptor family members . ^^^ Cells expressing ErbB 3 alone display a single class of low affinity HRG binding sites , whereas both high and low affinity binding sites can be measured on cells that co express both ErbB 3 and ErbB 2 . ^^^ Heregulin binding analysis revealed that a heterodimer composed of either ErbB 3 or ErbB 4 with ErbB 2 is sufficient for the formation of a high affinity binding state . ^^^ Further evidence for the unique specificity of ErbB 2 in generating this high affinity binding site was determined by inhibiting HRG binding with an ErbB 2 monoclonal antibody . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Time resolved fluorescence of the phenylalanine residue ( Phe ) alone and included in the transmembrane domain ( TMD ) sequences of the epidermal growth factor receptor ( EGFR ) and ErbB 2 was studied using the synchrotron radiation source of light , and compared to molecular dynamics ( MD ) simulations . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Recent studies have indicated that erbB 2 , a member of the epidermal growth factor receptor family , plays a pivotal role in epidermal growth , differentiation , and hair follicle morphogenesis . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 1 and ErbB 2 acquire distinct signaling properties dependent upon their dimerization partner . ^^^ To specifically examine dimerization dependent modulation of receptor signaling , we constructed NIH 3T3 cell lines expressing ErbB 1 and ErbB 2 singly and in pairwise combinations with each other ErbB family member . ^^^ The signaling properties of ErbB 2 following heterodimerization with the other ErbB receptors or homodimerization induced by point mutation or monoclonal antibody treatment were also analyzed . ^^^ ErbB 2 binding to peptides containing the Src homology 2 domain of Grb 2 or p 85 and the phosphotyrosine binding domain of Shc varied according to the mode of receptor activation . ^^^ Finally , tryptic phosphopeptide mapping of both ErbB 1 and ErbB 2 revealed that receptor phosphorylation is dependent on the dimerization partner . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 3 is a transmembrane signaling molecule that shares close structural homology with epidermal growth factor receptor ( EGFR ) , erbB 2 , and erbB 4 . ^^^ Because of some evidence that erbB 3 might interact with erbB 2 and EGFR , respectively , by heterodimerization , we also included erbB 2 and EGFR analysis with special regard to coexpression . ^^^ These findings indicate that erbB 2 and erbB 3 , but not EGFR , may contribute to tumor growth and disease progression in colon cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The four receptor tyrosine kinase 1 receptors , ErbB 1 , ErbB 2 , ErbB 3 , and ErbB 4 , which have been implicated in the development of a variety of normal and malignant tissues , are activated through ligand mediated homo and heterodimerization . ^^^ We have previously reported the frequent coexpression , heterodimerzation , and prognostic significance of ErbB 2 and ErbB 4 in childhood medulloblastoma , an embryonal tumor of the cerebellar external granule cell layer ( EGL ) . ^^^ In contrast , ErbB 2 , which is expressed in 86 % of medulloblastomas , could not be detected at any stage of cerebellar development . ^^^ Therefore , we propose that positive deregulation of ErbB 2 expression in the cerebellar EGL , leading to the formation of a NRG 41 beta driven ErbB 2 / ErbB 4 autocrine loop , is an important factor in medulloblastoma tumorigenesis . ^^^ In further support of this hypothesis , we provide evidence using reverse transcription PCR analysis that expression of the ErbB 2 and ErbB 4 receptors , but not ErbB 1 or ErbB 3 , is deregulated in medulloblastoma compared with normal developing cerebellum . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Specifically , NRG 2 alpha [ corrected ] , like NRG 1 beta [ corrected ] , emerges as a narrow specificity ligand , whereas NRG 2 beta [ corrected ] is a pan ErbB ligand that binds with different affinities to all receptor combinations , including those containing ErbB 1 , but excluding homodimers of ErbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Tyrosine phosphorylation of both EGFR and erbB 2 was detected in normal female BALB / c mice at 5 6 weeks of age , but not during the prepubertal stage , e . g . , 24 days of age . ^^^ Treatment of mice with estradiol or epidermal growth factor also stimulated the formation of mammary EGFR / erbB 2 phosphotyrosine . ^^^ Taken together , these data suggest that EGFR is essential for morphogenesis of the mammary ducts and functions during this period of mammary development as a heterodimer with erbB 2 in the mammary stroma . . ^^^ Activation and function of the epidermal growth factor receptor and erbB 2 during mammary gland morphogenesis . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Specific , irreversible inactivation of the epidermal growth factor receptor and erbB 2 , by a new class of tyrosine kinase inhibitor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In MDA MB 453 cells , both NRG1beta and NRG2beta stimulate the tyrosine phosphorylation of the ErbB 2 and ErbB 3 receptors to similar extents , but only NRG1beta potently stimulates morphological changes consistent with their differentiation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Bronchial mucosa biopsy specimens and brushings were analyzed for histopathologic changes , for immunohistopathologic expression of intermediate or surrogate end point markers that are linked to an increased risk of cancer ( Ki 67 [ a marker of cell proliferation ] , epidermal growth factor receptor , p 53 , Her 2 / neu [ also known as erbB 2 and ERBB 2 ] , globular actin , and abnormal DNA ploidy ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The agrin induced postsynaptic like apparatus also includes aggregates of the NRG receptors erbB 2 and erbB 3 as does postsynaptic apparatus at neuromuscular junctions . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
A relationship between histology , stage , erbB 1 , erbB 2 , ras and PD ECGF expression was not found . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
These include EGF receptor ( erbB 1 ) and erbB 4 when expressed individually and erbB 2 and erbB 3 when expressed together . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Here we report that the growth factors of Shope fibroma virus , Myxoma virus and vaccinia virus ( SFGF , MGF and VGF ) display unique patterns of specificity to ErbB receptor tyrosine kinases ; whereas SFGF is a broad specificity ligand , VGF binds primarily to ErbB 1 homodimers , and the exclusive receptor for MGF is a heterodimer comprised of ErbB 2 and ErbB 3 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
This suggests that the mutant EGF R signals through heterodimerization with endogenous , kinase active members of the EGF R family such as ErbB 2 or ErbB 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Unlike the EGFR and erbB 2 relatively little is known about the expression of erbB 4 in human tumours . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Affinity labeling experiments implied that a combination of ErbB 2 with ErbB 3 mediates the morphogenic signal of neuregulin in gastric cells . ^^^ Indeed , a similar morphogenic effect could be reconstituted in nonresponsive cells by coexpression of ErbB 2 and 3 . ^^^ We conclude that a heterodimer between the kinase defective neuregulin receptor , ErbB 3 , and the coreceptor , ErbB 2 , mediates the morphogenetic action of neuregulin . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Exogenous TGF alpha activated EGFR , ErbB 2 and MAPK , whereas EGF activated only the EGFR . ^^^ Other members are ErbB 2 , ErbB 3 , and ErbB 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Four of six pancreatic cancer cell lines exhibited the 6 . 2 kb erbB 3 mRNA transcript , and all four cell lines coexpressed the epidermal growth factor receptor and erbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In a panel of human tumor cell lines we analyzed expression of the receptor tyrosine kinases EGFR , ErbB 2 and ErbB 3 , and the response to TNF alpha . ^^^ Among the cell lines tested those resistant to TNF alpha were found to express high levels of either EGFR , or ErbB 2 and ErbB 3 . ^^^ In TNF sensitive breast and cervical carcinoma cells activation of EGFR or ErbB 2 by the exogenous growth factors EGF and heregulin beta 1 resulted in a significant increase in the number of cells surviving TNF alpha treatment . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The human epidermal growth factor receptor ( HER or ErbB ) family consists of four distinct members , including the epidermal growth factor ( EGF ) receptor ( EGFR , HER 1 , or ErbB 1 ) , ErbB 2 ( HER 2 or neu ) , ErbB 3 ( HER 3 ) , and ErbB 4 ( HER 4 ) . ^^^ Binding of a specific ligand to one of the ErbB receptors triggers the formation of specific receptor homo and heterodimers , with ErbB 2 being the preferred signaling partner . ^^^ All cell lines examined expressed detectable levels of ErbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We previously described spatiotemporal expression of various epidermal growth factor ( EGF ) like ligands and receptor subtypes , ErbB 1 and ErbB 2 , during the peri implantation period . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Amplification of erbB 4 oncogene occurs less frequently than that of erbB 2 in primary human breast cancer . ^^^ We therefore used the double differential polymerase chain reaction ( ddPCR ) for determination of the amplification profile of erbB 4 and erbB 2 , another gene from the ErbB family , in human primary breast cancer specimens . ^^^ Amplification of erbB 2 was detected in 19 % and erbB 4 in 13 % of the samples studied . ^^^ Human breast cancer derived cell lines in most cases overexpress both erbB 2 and erbB 4 ( Beerli et al . , 1995 . ^^^ USA 92 , 9747 9751 ) , but data on separate erbB 2 overexpression , without overexpression of erbB 4 , were also reported ( Wosikowski et al . , 1997 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Although the role of oncogenes and growth factors in prostate carcinoma is still unclear , overexpression of the epidermal growth factor receptor ( erbB 1 ) and the proto oncogene erbB 2 have been reported in prostate tumors , and erbB 2 related to poor prognosis and distant metastasis . ^^^ Gains of the relative genomic content of erbB 1 and erbB 2 in prostate carcinoma and their association with metastasis . ^^^ Recent allelotyping studies in prostate cancer have shown chromosomal gains in 7p and 17q , regions where erbB 1 and erbB 2 are localized respectively , although no direct evidence of an increased gene copy number of either erbB 1 or erbB 2 has been reported . ^^^ No gains of erbB 1 or erbB 2 genomic content were detected in the BPH samples . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
By immunoprecipitation followed by Western blotting we showed that ErbB1 / ErbB3 heterodimers are the major mitogenic signaling entity in 1 , 25 ( OH ) 2D3 stimulated cells . 1 , 25 ( OH ) 2D3 did not affect the levels of the proteoglycan dependent EGFR ligands amphiregulin and heparin binding EGF nor the synthesis of proteoglycans , as assessed by 35S labeling and ion exchange chromatography . 1 , 25 ( OH ) 2D3 caused a marked increase in the cellular contents of ErbB 1 , ErbB 2 , and ErbB 3 proteins . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Overall , serum positivity was most frequently directed against ErbB 2 followed by EGFR , ErbB 3 and ErbB 4 . ^^^ Moreover , approximately half of the positive sera exhibited concomitant reactivity with multiple ErbB receptors including EGFR and ErbB 2 , EGFR and ErbB 4 , ErbB 2 and ErbB 3 or EGFR , ErbB 2 and ErbB 3 . ^^^ These findings implicate multiple ErbB receptors including ErbB 3 and ErbB 4 in addition to EGFR and ErbB 2 in primary human cancer . ^^^ Specificity patterns comprised tumor patients with unique serum reactivity against ErbB 2 or ErbB 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Growth inhibition of breast cancer cells by Grb 2 downregulation is correlated with inactivation of mitogen activated protein kinase in EGFR , but not in ErbB 2 , cells . ^^^ Increased breast cancer growth has been associated with increased expression of epidermal growth factor receptor ( EGFR ) and ErbB 2 receptor tyrosine kinases ( RTKs ) . ^^^ Grb 2 is important for the transformation of fibroblasts by EGFR and ErbB 2 ; however , whether Grb 2 is also important for the proliferation of breast cancer cells expressing these RTKs is unclear . ^^^ Grb 2 inhibition led to MAP kinase inactivation in EGFR , but not in ErbB 2 , breast cancer cells , suggesting that different pathways might be used by EGFR and ErbB 2 to regulate breast cancer growth . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
EGFR CD 533 expression inhibits radiation and EGF induced EGFR autophosphorylation and MAPK activation and , therefore , functions as a dominant negative mutant without blocking the expression of EGFR or erbB 2 , another member of the erbB receptor Tyr kinase family . ^^^ EGFR CD 533 expression inhibits radiation and EGF induced EGFR autophosphorylation and MAPK activation and , therefore , functions as a dominant negative mutant without blocking the expression of EGFR or erbB 2 , another member of the erbB receptor Tyr kinase family . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The epidermal growth factor ( EGF ) receptor ( EGFR ) family includes four homologous transmembrane receptor protein tyrosine kinases , EGFR , ErbB 2 , ErbB 3 , and ErbB 4 . ^^^ Here , we show that EGF stimulates activation of EGFR and transactivation of ErbB 2 in quiescent HASM cells . ^^^ Betacellulin , a ligand for EGFR , ErbB 3 , and ErbB 4 , induced DNA synthesis of HASM cells and stimulated signaling through the activation of EGFR and ErbB 2 but not of ErbB 3 and ErbB 4 . ^^^ Despite the mRNA and protein expression of all members of the EGFR family , ligand stimulated signaling induced activation of EGFR and ErbB 2 but not of ErbB 3 and ErbB 4 . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The erbB 4 gene encodes a detected receptor protein that possesses intrinsic tyrosine kinase activity and belongs to the family of the epidermal growth factor receptor ( EGFR ) ; erbB 4 is stimulated by the heregulins and betacellulin , which enables this receptor to form heterodimers with erbB 2 , a prerequisite for erbB 2 activation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Here we use isoform specific EGFR and ErbB 2 antibodies to show that the duration of EGFR signalling induced by a single TGFalpha exposure is less than that induced by equimolar EGF . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 2 / HER2 is an important signaling partner for the epidermal growth factor receptor ( EGFR ) . ^^^ To investigate how erbB 2 amplification affects its interactions with the EGFR , we used a human mammary epithelial cell system in which erbB 2 expression was increased 7 20 fold by gene transfection . ^^^ We found that amplification of erbB 2 caused constitutive activation of erbB 2 as well as ligand independent activation of the EGFR . ^^^ Overexpression of erbB 2 strongly inhibited erbB 2 down regulation following transactivation by EGFR . ^^^ Significantly , down regulation of activated EGFR was also inhibited by erbB 2 amplification , resulting in enhanced ligand dependent activation of the EGFR . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In contrast , EGFR truncation did not impair EGF mitogenic signaling , and in c ' 1000 cells EGF was able to stimulate the association of ErbB 2 with GRB 2 and SHC . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
AIM : The type 1 family of growth factor receptors includes ErbB 1 , ErbB 2 , ErbB 3 , and ErbB 4 which are frequently overexpressed in various human cancer cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The mRNA level of erbB 2 , erbB 3 , rapsyn , MuSK , SHP 2 and beta actin remained unchanged in response to ARIA stimulation in C2C12 cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
HRG can bind to receptor tyrosine kinases erbB 3 and erbB 4 , thereby inducing erbB 3 and erbB 4 heterodimerization with erbB 2 , leading to receptor tyrosine phosphorylation and activating downstream signal transduction . ^^^ While investigating the downstream signals involved in HRG beta 1 enhanced cell aggregation , we observed that HRG beta 1 induced tyrosine phosphorylation of erbB 2 and crbB 3 receptor heterodimers and increased the association of the dimerized receptors with the 85 kDa subunit of phosphatidylinositol 3 kinase ( PI3K ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
These studies also revealed that ErbB 2 preferentially enhances ligand binding to ErbB 3 or ErbB 4 and to a lesser degree to ErbB1 . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The receptors erbB 3 and erbB 4 are members of the type 1 tyrosine kinase receptor family which also comprises epidermal growth factor receptor ( EGF R ) and erbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Epidermal growth factor ( EGF ) stimulates the homodimerization of EGF receptor ( EGFR ) and the heterodimerization of EGFR and ErbB 2 . ^^^ It is unclear how the EGFR ErbB 2 heterodimers might behave . ^^^ In this research , we showed by subcellular fractionation , immunoprecipitation , Western blotting , indirect immunofluorescence , and microinjection that , in the four breast cancer cell lines MDA 453 , SKBR 3 , BT 474 , and BT 20 , the EGFR ErbB 2 heterodimerization levels were positively correlated with the ratio of ErbB2 / EGFR expression levels . ^^^ Moreover , in MDA 453 , SKBR 3 , and BT 474 cells , which have very high levels of EGFR ErbB 2 heterodimerization , EGF induced EGFR endocytosis was greatly inhibited compared with that in BT 20 cells , which have a very low level of EGFR ErbB 2 heterodimerization . ^^^ Microinjection of an ErbB 2 expression plasmid into BT 20 cells significantly inhibited EGF stimulated EGFR endocytosis . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 2 homodimerizes but also presents as a common auxiliary subunit of the EGF and heregulin receptors ( erbB 1 or EGFR ; and erbB 3 4 , respectively ) , with which it heteroassociates . ^^^ The EGF induced increase in the erbB 2 cluster size was inhibited by the EGFR specific tyrosine kinase inhibitor PD 153035 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
While all lines expressed variable amounts of each receptor , erbB 3 and to a lesser extent erbB 2 were constitutively tyrosine phosphorylated in all lines . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Epidermal growth factor ( EGF ) receptor tyrosine kinases include ErbB 1 , ErbB 2 , ErbB 3 and ErbB 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In this report we show that ErbB 2 , ErbB 3 , and ErbB 4 do not potentiate Stat 5 phosphorylation by EGF . ^^^ However , neu differentiation factor induced heterodimers of ErbB 2 and ErbB 4 activated Stat 5 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Paradoxically , the neuregulin receptor ErbB 3 is devoid of catalytic activity , but its heterodimerization with other ErbBs , particularly the ligand less ErbB 2 oncoprotein of carcinomas , reconstitutes superior mitogenic and transforming activities . ^^^ Consistent with the possibility that this domain recruits a relatively potent signaling pathway ( s ) , the mitogenic signals generated by the recombinant fusion protein were superior to those generated by ErbB 1 homodimers and comparable to the proliferative activity of ErbB 2 / ErbB 3 heterodimers . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Here we show that PKC dependent transmodulation of EGFR and ErbB 2 signalling is schedule specific : prolonged pre treatment of A 431 cells with the PKC agonist phorbol dibutyrate potently inhibits subsequent ligand induced EGFR signalling as expected , but EGF pre treatment reverses the inhibitory effect of phorbol . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 2 transgene induction was accompanied by increased expression of TGFalpha , a ligand of epidermal growth factor receptor ( EGFR ) , and to a lesser extent , EGFR , further enhancing RTK signal transduction . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Ligand dependence of cell growth and MAP kinase signaling are retained in epidermal growth factor receptor ( EGFR ) transfectants but are abolished in ErbB 2 expressing cells , which grow and signal constitutively . ^^^ In association with this phenomenon , we have noticed that ErbB 2 expressing cells contain increased amounts of EGFR , which is hyperphosphorylated . ^^^ EGFR overexpressors do not contain increased levels of ErbB 2 , however , tending to exclude a transfection artifact caused by saturation of receptor processing . ^^^ EGF treatment of EGFR transfectants results in more rapid EGFR downregulation than occurs in ErbB 2 transfectants , but Northern blot analysis demonstrates reduced basal EGFR gene expression in ErbB 2 transfectants . ^^^ We conclude that ErbB 2 expression impairs EGFR downregulation via a posttranscriptional mechanism and propose that ErbB 2 overexpression may sensitize tumor cells to the mitogenic effects of heterologous growth factors by retarding degradation of liganded heterodimers . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Differential expression of erbB 2 and erbB 4 receptors . ^^^ METHODS AND RESULTS : We used ribonuclease protection assays to quantify mRNA levels of neuregulin , erbB 2 , and erbB 4 in left ventricular ( LV ) tissue and myocytes of normal rats and rats with aortic stenosis with pressure overload hypertrophy 6 and 22 weeks after banding . ^^^ LV erbB 2 and erbB 4 message levels in LV tissue and myocytes were maintained during early compensatory hypertrophy in 6 week aortic stenosis animals compared with age matched controls ; in contrast , erbB 2 and erbB 4 message levels were depressed in 22 week aortic stenosis animals at the stage of early failure ( both P < 0 . 01 vs age matched controls ) . ^^^ Immunoblotting of erbB 2 and erbB 4 also showed normal protein levels in 6 week aortic stenosis animals compared with controls ; however , erbB 2 and erbB 4 protein levels were depressed in 22 week aortic stenosis animals ( 48 % decrease in erbB 2 , P < 0 . 05 , and 43 % decrease in erbB 4 , P < 0 . 01 ) relative to age matched controls . ^^^ CONCLUSIONS : The neuregulin receptors erbB 2 and erbB 4 are downregulated at both the message and protein levels at the stage of early failure in animals with chronic hypertrophy secondary to aortic stenosis . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We recently demonstrated that human lung epithelial cells , overexpressing ErbB 2 , formed tumors in nude mice only when high levels of transforming growth factor alpha ( TGFalpha ) were produced . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The level of immunostaining was correlated with the clinico pathological characteristics of the endometrial carcinoma patients and with the parallel expression of the epidermal growth factor receptor ( EGFR ) and erbB 2 . ^^^ Expression of keratinocyte growth factor receptor compared with that of epidermal growth factor receptor and erbB 2 in endometrial adenocarcinoma . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
These genetic alterations include gene amplification and overexpression of oncogenes such as myc , erbB 2 , EGFR and cyclinD 1 and mutations , deletions and hypermethylation leading to p 16 and TP 53 tumor suppressor gene inactivation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Two closely related receptors , the epidermal growth factor receptor ( EGFR ) and ErbB 2 , are overexpressed in a significant percentage of breast and prostate carcinomas , among others , with this up regulated signaling correlating with tumor progression . ^^^ Therefore , we investigated whether this PLCgamma signaling pathway also was rate limiting for invasion in other tumor cell lines and types and whether this EGFR activity is subsumed by the closely related ErbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Although ligand engagement of the EGFR stimulated modest beta 1 dependent increases in cell adhesion and motility , heregulin beta ( HRGbeta ) binding to the erbB 3 receptor initiated rapid and potent induction of breast carcinoma cell adhesion and migration and required dimerization of erbB 3 with erbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
OBJECTIVE : To determine the feasibility and the economic impact of tumour EGFR , erbB 2 and cathepsin D measurements in women with node negative breast cancer . ^^^ DESIGN : Consecutive tumour samples received at a regional steroid receptor laboratory from patients with node negative breast cancer were evaluated with commercially available kits to determine EGFR , erbB 2 and cathepsin D levels . ^^^ Epidermal growth factor receptor ( EGFR ) positivity ( > 10 fmol / mg protein ) was found in 16 . 3 % of patients , with 19 . 9 % of patients positive for erbB 2 ( > 250 units / mg protein ) and 17 . 3 % positive for cathepsin D ( > 70 pmol / mg protein ) . ^^^ Prospective clinical trials incorporating tumour EGFR , erbB 2 and cathepsin D are feasible and economically viable . . ^^^ Tumour epidermal growth factor receptor , erbB 2 and cathepsin D in node negative invasive breast cancer : their impact on the selection of patients for systemic adjuvant therapy . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
AP 1510 treatment induced tyrosine phosphorylation of ErbB 1 and ErbB 2 homodimers and recruitment of Src homology 2 domain containing proteins ( Shc and Grb 2 ) . ^^^ In addition , ErbB 1 and ErbB 2 homodimers activated downstream signaling pathways leading to Erk 2 and Akt phosphorylation . ^^^ Cells expressing AP 1510 induced ErbB 1 homodimers were able to form foci ; however , cells expressing ErbB 2 homodimers displayed a five to sevenfold higher focus forming ability . ^^^ Using rapamycin inducible heterodimerization we show that c Cbl is unable to associate with ErbB 1 in a ErbB 1 ErbB2 heterodimer most likely because ErbB 2 is unable to phosphorylate the c Cbl binding site on ErbB 1 . ^^^ Thus , we demonstrate that ErbB 1 and ErbB 2 homodimers differ in their abilities to transform fibroblasts and provide evidence for differential signaling by ErbB homodimers and heterodimers . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Inhibitors with acrylamides at these positions proved to be irreversible alkylating agents for both EGFr and erbB 2 with cellular inhibitory activities in the low nanomolar range , and very potent in vivo antitumour activity . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The ErbB 2 tyrosine kinase functions as coreceptor for the neuregulin receptors ErbB 3 and ErbB 4 and can participate in signaling of EGF receptor ( ErbB 1 ) , interleukin receptor gp 130 , and G protein coupled receptors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Neuregulin stimulates ErbB 2 , ErbB 3 , and ErbB 4 , members of the ErbB family of receptor tyrosine kinases . ^^^ We found that SHP 2 interacted with ErbB 2 and ErbB 3 after neuregulin stimulation of muscle cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
HRG alpha activated tyrosine phosphorylation of epidermal growth factor receptor ( EGFR ) , erbB 2 , and erbB 3 and induced not only erbB3 / erbB2 but also erbB3 / EGFR and erbB2 / EGFR heterodimer formation in MKN 28 cancer cells . ^^^ Expression of heregulin alpha , erbB 2 , and erbB 3 and their influences on proliferation of gastric epithelial cells . ^^^ RESULTS : Cancer cell lines and rat epithelial cells expressed erbB 2 and erbB 3 , but protein expression of erbB 4 was not detected . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
No effects were observed in estrogen receptor negative ( ER ) MDA MB 453 cells , which express low levels of endogenous ErbB 4 and high levels of ErbB 2 and ErbB 3 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
By in situ hybridization and immunohistochemical staining , the expression of ErbB 3 as well as that of ErbB 2 , a coreceptor for ErbB 3 , was detected in PGCs in genital ridges at 12 . 5 dpc ( days postcoitum ) . ^^^ Neuregulin beta , a ligand for ErbB 2 and ErbB 3 , was also expressed in genital ridges . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
However , most of the clinical data relate to ErbB 2 , a protein whose overexpression in subsets of carcinomas can predict poor prognosis . ^^^ Although no ligand has so far been assigned to ErbB 2 , recent biochemical evidence implies that this oncoprotein operates as a shared receptor subunit of other ErbBs . ^^^ Several biochemical attributes enable ErbB 2 to act as an epithelial cell amplifier of stroma derived growth factor signals : It delays ligand dissociation , enhances coupling to the mitogen activated protein kinase pathway , and impedes the rate of receptor downregulation . ^^^ The realization that ErbB 2 is a master regulator of a signaling network that drives epithelial cell proliferation identifies this protein as a target for cancer therapy . ^^^ Indeed , various ErbB 2 directed therapeutic approaches , including immunological and genetic therapies , demonstrate promising clinical potential . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The aim of this study was to determine whether human epidermal growth factor receptor 2 ( HER 2 ) / erbB 2 , p glycoprotein , or p 53 expression correlated with histologic response to preoperative chemotherapy or event free survival . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Reverse transcription polymerase chain reaction analysis also demonstrated ErbB 2 and ErbB 3 expression in human bladder muscle tissue , suggesting the possibility of receptor cross talk after ErbB 1 activation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Neuregulin increases the association of the adaptor proteins Grb 2 and Shc with both ErbB 2 and ErbB 3 in C2C12 muscle cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We demonstrate that ErbB 2 ( neu ) , ErbB 3 , and ErbB 4 are highly expressed , whereas ErbB 1 ( EGF r ) is undetectable . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunoprecipitation / Western blot studies revealed that HRG ( 100 ng / ml ) stimulated tyrosine phosphorylation and dimerization of ErbB 3 and ErbB 2 , but had no effect on phosphorylation of the EGFR . ^^^ Further studies revealed that , while both EGF ( 100 ng / ml ) and CCh ( 100 microM ) stimulated phosphorylation of the EGFR , only EGF stimulated phosphorylation of ErbB 2 , and neither stimulated ErbB 3 phosphorylation . ^^^ EGF , but not CCh , stimulated the formation of EGFR / ErbB2 receptor dimers and the recruitment of p 85 to ErbB 2 . ^^^ ErbB 2 and ErbB 3 receptors mediate inhibition of calcium dependent chloride secretion in colonic epithelial cells . ^^^ We conclude that ErbB 2 and ErbB 3 are expressed in T ( 84 ) cells and are functionally coupled to inhibition of calcium dependent chloride secretion . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Neuregulins signaling via a glial erbB 2 erbB 4 receptor complex contribute to the neuroendocrine control of mammalian sexual development . ^^^ Here , we show that activation of astrocytic erbB 2 / erbB 4 receptors plays a significant role in the process by which the hypothalamus controls the advent of mammalian sexual maturation . ^^^ Hypothalamic astrocytes express both the erbB 2 and erbB 4 genes , but no erbB 3 , and respond to neuregulins ( NRGs ) by releasing prostaglandin E ( 2 ) ( PGE ( 2 ) ) , which acts on neurosecretory neurons to stimulate secretion of luteinizing hormone releasing hormone ( LHRH ) , the neuropeptide controlling sexual development . ^^^ The actions of TGFalpha and NRGs in glia are synergistic and involve recruitment of erbB 2 as a coreceptor , via erbB 1 and erbB 4 , respectively . ^^^ Hypothalamic expression of both erbB 2 and erbB 4 increases first in a gonad independent manner before the onset of puberty , and then , at the time of puberty , in a sex steroid dependent manner . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
However the kinase activity of erbB 2 can be activated without any ligand , if it is overexpressed , and by heteroassociation with other members of the erbB family ( erbB 1 or epidermal growth factor receptor , erbB 3 and erbB 4 ) . ^^^ Complexity of signal transduction mediated by ErbB 2 : clues to the potential of receptor targeted cancer therapy . ^^^ The erbB 2 oncogene belongs to the type 1 trans membrane tyrosine kinase family of receptors . ^^^ This review will focus on the signal transduction through this protein , and explains how the overexpression of erbB 2 may result in poor prognosis of breast cancer , and finally it will summerize our current understanding about the therapeutic potential of receptor targeted therapy in breast cancer . ^^^ ErbB 2 does not have any known ligand which is able to bind to it with high affinity . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In human breast cancer , lack of response to endocrine therapy is often associated with decreased expression of the estrogen receptor and increased expression of epidermal growth factor receptor ( EGFR ) and / or HER 2 / neu ( ErbB 2 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 2 is necessary for induction of carcinoma cell invasion by ErbB family receptor tyrosine kinases . ^^^ In this study , we utilize carcinoma cells depleted of ErbB 2 , but not other ErbB receptor members , to specifically examine the role of ErbB 2 in carcinoma cell migration and invasion . ^^^ Cells stimulated with EGF related peptides show increased invasion of the extracellular matrix , whereas cells devoid of functional ErbB 2 receptors do not . ^^^ ErbB 2 facilitates cell invasion through extracellular regulated kinase ( ERK ) activation and coupling of the adaptor proteins , p130CAS and c CrkII , which regulate the actin myosin cytoskeleton of migratory cells . ^^^ Overexpression of ErbB 2 in cells devoid of other ErbB receptor members is sufficient to promote ERK activation and CAS / Crk coupling , leading to cell migration . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Changes in ErbB 2 ( her 2 / neu ) , ErbB 3 , and ErbB 4 during growth , differentiation , and apoptosis of normal rat mammary epithelial cells . ^^^ Studies were undertaken to examine the natural role of ErbB 2 , ErbB 3 , and ErbB 4 during the development of normal rat mammary epithelial cells ( MECs ) in vivo and in vitro . ^^^ Immunohistochemical analysis demonstrated that mammary gland terminal end buds expressed abundant ErbB 2 and ErbB 4 but limited ErbB 3 in pubescent rats , whereas luminal epithelial cells in nulliparous rats expressed ErbB 2 , ErbB 3 , and / or ErbB 4 . ^^^ During pregnancy , ductal epithelial cells and stromal cells expressed abundant ErbB 3 but limited ErbB 2 . ^^^ Although ErbB 2 and ErbB 3 were downregulated throughout lactation , both receptors were re expressed during involution . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Aberrations of erbB 1 and erbB 2 oncogenes in non dysplastic leukoplakias of the oral cavity . ^^^ The purpose of this study was to analyse erbB 1 and erbB 2 oncogenes in non dysplastic oral leukoplakia to see if we could pinpoint the first steps towards dysplasia and possible carcinogenesis . ^^^ The mean gene copy numbers of erbB 1 and erbB 2 were calculated from the formula to compare the absolute quantities of reference gene and oncogene from 24 patients who did not have leukoplakia . ^^^ In eight patients with leukoplakias , the results indicated aberrations of the erbB 1 oncogene , and two patients had gene dosage changes of erbB 2 . ^^^ These results suggest that aberrations of erbB 1 and erbB 2 are additional markers in premalignant oral lesions at the beginning of the carcinogenic process , and that genetic alterations in histologically non dysplastic premalignant oral lesions are common . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Human white matter from non neurologic cases , multiple sclerosis ( MS ) and other neurologic diseases ( OND , inflammatory and non inflammatory ) , was subjected to immunocytochemistry and Western blotting for expression of the neuregulin , glial growth factor 2 ( GGF 2 ) , and its receptors , erbB 2 , erbB 3 and erbB 4 . ^^^ In human lymph node tissue , some lymphocytes were positive for erbB 2 , erbB 3 and erbB 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Oncogenes with potential prognostic significance identified in bladder cancer the RAS family , epidermal growth factor receptor , ERBB 2 , MDM 2 , and cyclin D 1 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The epidermal growth factor receptor family consists of four related tyrosine kinases : the epidermal growth factor receptor ( EGF R or ErbB ) , ErbB 2 , ErbB 3 , and ErbB 4 . ^^^ Since EGF R is expressed by proliferating cells in the central nervous system ( CNS ) , including multipotent CNS stem cells , we examined the expression of ErbB 2 , ErbB 3 and ErbB 4 in the germinal epithelia of the developing rat brain using in situ hybridization . ^^^ Expression of the EGF receptor family members ErbB 2 , ErbB 3 , and ErbB 4 in germinal zones of the developing brain and in neurosphere cultures containing CNS stem cells . ^^^ ErbB 2 and ErbB 4 mRNAs were widely distributed within the germinal zones as early as E 12 . ^^^ However , as development proceeded , ErbB 2 mRNA was mainly present within the layers of cells immediately adjacent to the ventricular surface the ventricular zone , while ErbB 4 mRNA was predominantly expressed by subventricular zone cells , in the regions where these specialized germinal epithelia were present . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We have ectopically expressed various ErbB receptors in 32D myeloid cells lacking endogenous ErbB proteins , and in CHO cells , which express only ErbB 2 . ^^^ We show here that activation of ErbB 3 / ErbB 2 heterodimeric receptors triggers PI 3 kinase dependent lamellipodia formation and spreading , while individual ErbB receptor homodimers as well as ErbB 3 / ErbB 1 heterodimers are much less effective . ^^^ CHO cells expressing ErB 3 / ErbB 2 together with N cadherin , an adhesion receptor , form epithelioid colonies . ^^^ Transactivation of ErbB 2 is not sufficient for the activation of cell motility and ring formation , and the C terminal domain of ErbB 3 bearing the docking sites for the p 85 subunit of PI 3 kinase is essential for these morphogenetic effects . ^^^ Thus , ErbB 3 in conjunction with ErbB 2 mediates , via its C terminal domain , cytoskeletal and adhesion alterations which activate cell spreading and motility , leading to the formation of complex structures such as multicellular rings . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
A series of monoclonal antibodies ( MAbs ) 3 directed against the EGF ( ErbB 1 ) receptor and the closely related HER2 / Neu ( ErbB 2 ) receptor are currently under evaluation . ^^^ Clinical activity with one of these antibodies , trastuzumab , a humanized anti ErbB 2 MAb , has been documented in patients with breast cancer in a series of clinical trials and has recently been approved for the therapy of patients with metastatic ErbB 2 overexpressing breast cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunohistochemical analyses of p 53 , epidermal growth factor receptor , erbB 2 , erbB 3 , erbB 4 , and Bcl 2 expression were performed . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Overexpression of the ErbB 2 and epidermal growth factor receptor ( EGFR ) tyrosine kinases is frequently observed in squamous cell carcinomas of the head and neck , and has been correlated with shorter overall survival . ^^^ By immunoblot analysis , we have found EGFR and ErbB 2 expression in 6 out of 6 established head and neck cancer cell lines . ^^^ Elevated EGFR protein levels were noted in 3 and elevated ErbB 2 levels in 5 of them . ^^^ Significant expression of EGFR and ErbB 2 was also detected in 17 of 47 and 26 of 45 primary tumor samples . ^^^ We have analyzed the antitumoral activity of recombinant single chain antibody toxins specific for ErbB 2 and EGFR against head and neck cancer cells in vitro and in vivo . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
These studies demonstrate significant expression of the ErbB 2 , ErbB 3 , and ErbB 4 receptors , in addition to heregulin isoforms , in the developing murine fetal pancreas . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
A panel of nine molecular markers was chosen for immunohistochemical analysis of the tumor : recessive oncogenes p 53 and bcl 2 , the protooncogene erbB 2 , KI 67 proliferation index , retinoblastoma oncogene ( Rb ) , epidermal growth factor receptor ( EGFr ) , angiogenesis factor 8 , sialyl Tn antigen ( STN ) , and CD 44 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The compounds were evaluated for their inhibition of phosphorylation of the isolated EGFR enzyme and for inhibition of EGF stimulated autophosphorylation of EGFR in A 431 cells and of heregulin stimulated autophosphorylation of erbB 2 in MDA MB 453 cells . ^^^ Quinazoline analogues with 7 alkoxyamine solubilizing groups were potent irreversible inhibitors of the isolated EGFR enzyme , with IC ( 50 [ app ] ) values from 2 to 4 nM , and potently inhibited both EGFR and erbB 2 autophosphorylation in cells . 7 Alkylamino and 7 alkoxyaminopyrido [ 3 , 2 d ] pyrimidines were also irreversible inhibitors with equal or superior potency against the isolated enzyme but were less effective in the cellular autophosphorylation assays . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 2 potentiates breast tumor proliferation through modulation of p 27 ( Kip 1 ) Cdk 2 complex formation : receptor overexpression does not determine growth dependency . ^^^ Overexpression of the ErbB 2 receptor , a major component of the ErbB receptor signaling network , contributes to the development of a number of human cancers . ^^^ ErbB 2 presents itself , therefore , as a target for antibody mediated therapies . ^^^ In this respect , anti ErbB 2 monoclonal antibody 4D5 specifically inhibits the growth of tumor cells overexpressing ErbB 2 . ^^^ We have analyzed the effect of 4D5 mediated ErbB 2 inhibition on the cell cycle of the breast tumor cell line BT 474 . 4D5 treatment of BT 474 cells resulted in a G ( 1 ) arrest , preceded by rapid dephosphorylation of ErbB 2 , inhibition of cytoplasmic signal transduction pathways , accumulation of the cyclin dependent kinase inhibitor p 27 ( Kip 1 ) , and inactivation of cyclin Cdk 2 complexes . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Heregulin , but not ErbB 2 or ErbB 3 , heterozygous mutant mice exhibit hyperactivity in multiple behavioral tasks . ^^^ To investigate this the heregulin 1 , ErbB 2 , or ErbB 3 locus was disrupted in a targeted manner and mice heterozygous for the mutation were analyzed . ^^^ ErbB 2 and ErbB 3 mutant mice , whose strain origin was identical to that of heregulin mutants , showed no sign of the behavioral alterations . ^^^ It is suggested that the abnormalities seen in heregulin mutant mice are due to mutation at that locus and the lack of alterations seen in ErbB 2 and ErbB 3 mutant mice is the result of compensation by unaltered sister receptors . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : To investigate the expression of type 1 growth factor receptors ( epidermal growth factor receptor , ErbB 2 , and ErbB 3 ) in the conjunctival epithelium of patients with keratoconjunctivitis sicca . ^^^ METHODS : Immunofluorescent staining and Western blotting were performed to grade the level of expression of the epidermal growth factor receptor ErbB 2 , and ErbB 3 in conjunctival epithelial impression cytologies taken from both eyes of seven normal subjects and 22 patients with keratoconjunctivitis sicca . ^^^ Immunofluorescent staining scores for these receptors were correlated with conjunctival lissamine green staining scores ( r = . 574 , P < . 01 for epidermal growth factor receptor ; r = . 620 , P < . 0025 for ErbB 2 ; r = . 502 , P < . 025 for ErbB 3 ) and with corneal fluorescein staining ( r = . 409 , P < . 05 for ErbB 2 ; r = . 588 , P < . 005 for ErbB 3 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The expression of erbB 2 / HER 2 , p 53 , ras and epidermal growth factor receptor ( EGFR ) was also detected by immunohistochemistry and protein blotting . ^^^ Coexpression of erbB 2 , pan ras , p 53 and EGFR internal and external domains was significantly higher in cancer cells than in normal mucosa . ^^^ Overexpression of erbB 2 and EGFR was associated with a poor prognosis . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Neural and thymus derived activator for ErbB kinases ( NTAK ) is a recently described member of the neuregulin family that binds directly to ErbB 3 and ErbB 4 and transactivates ErbB 2 . ^^^ Although both NTAKs induce the highest level of tyrosine phosphorylation of ErbB 2 , NTAKalpha2a and NTAKbeta preferentially induce ErbB 3 and ErbB 4 phosphorylation , respectively . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The ErbB receptor tyrosine kinase family consists of the epidermal growth factor ( EGF ) receptor ( ErbB 1 ) and three related receptors ( ErbB 2 , ErbB 3 , ErbB 4 ) . ^^^ Overexpression of ErbB 1 , ErbB 2 and ErbB 4 receptors was enough to activate them as judged by their phosphorylation , whereas co expression of other ErbB receptors was necessary for the phosphorylation of the ErbB 3 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Evidence is provided for trophoblast cell expression of epidermal growth factor receptor ( EGFR ) , ErbB 2 , fibroblast growth factor receptor 1 ( FGFR 1 ) , transforming growth factor alpha , and heparin binding EGF . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
To date , no ligand for ErbB 2 has been identified , and comparison of the extracellular domains of ErbB 2 reveals two regions that are not conserved across the mammalian species . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Furthermore , only the ErbB 2 inhibitor AG 879 , but not the EGFR inhibitor AG 1478 , abolishes androgen induced cell proliferation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The transphosphorylation specifically takes place for the receptor subfamily , as it is not observed between Met or Ron and ErbB 1 , ErbB 2 or TrkA . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We have identified a new PDZ protein we named ERBIN ( ERBB 2 interacting protein ) that acts as an adaptor for the receptor ERBB2 / HER2 in epithelia . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Certain ligands and receptors of the family , especially the ErbB 2 receptor tyrosine kinase , contribute to a relatively virulent phenotype of some human tumors ; most notable are carcinomas of secretory epithelia . ^^^ ErbB 2 emerges as a master coordinator of the network , prolonging and amplifying signaling by decelerating the dissociation rates of its heterologous ligands . ^^^ Thus , the tumorigenic action of ErbB 2 may be attributed to its ability to act as a shared signaling subunit , rather than by functioning as a bone fide receptor . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
To assess whether ErbB 2 is a critical component in epidermal growth factor ( EGF ) mediated stimulation of tumor cell proliferation , we used as a model SK OV 3 ovarian cancer cells , which over express EGF receptor ( EGFR ) and ErbB 2 receptors . ^^^ The induction of colony formation by EGF was completely abrogated in ErbB 2 depleted cells , despite unchanged expression levels and tyrosine phosphorylation of the EGFR . ^^^ Our results demonstrate that in human ovarian cancer cells the EGFR ErbB 2 heterodimer , and not the EGFR homodimer , can be rate limiting for EGF mediated proliferation , thus suggesting that the oncogenic activity of ErbB 2 in human tumors is due in part to its ability to increase the growth response to stroma derived EGF like growth factors . . ^^^ ERbB 2 expression is rate limiting for epidermal growth factor mediated stimulation of ovarian cancer cell proliferation . ^^^ Over expression of the ErbB 2 proto oncogene frequently coincides with an aggressive clinical course of certain human adenocarcinomas . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Geldanamycin ( GA ) and herbimycin ( HA ) , specific inhibitors of the cytosolic chaperone HSP 90 and its endoplasmic reticulum homologue GRP 94 , were shown to accelerate degradation of the EGF R and of its homologue p 185 ( c ) ( erbB 2 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 2 amplification with a gene copy number > 1 . 6 in tumour tissue and erbB 1 deletion with a gene copy number < 0 . 4 in tumour surrounding mucosa are of clinical relevance and indicate an early tumour recurrence or metastasis ( p < 0 . 05 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
TaqMan quantitative RT PCR analysis and immunocytochemistry reveal that heregulin and its binding receptors ( ErbB 2 , ErbB 3 and ErbB 4 ) are expressed in the inner ear sensory epithelium . ^^^ Because neuregulin 3 that signals only through ErbB 4 does not show an effect , these data suggest that activation of the ErbB 2 ErbB 3 heterodimeric complexes , rather than ErbB 4 , is critical for the proliferative response in the utricular sensory epithelium . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The mechanism by which EGFR recruits the PI3K / Akt pathway was in part differentially regulated at the level of Ras but independent of heterodimerization of EGFR with either ErbB 2 or ErbB 3 based upon functional dissection of pathways in esophageal cancer cell lines . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The expression of four protein tyrosine kinase receptors ( EGFR , ErbB 2 , ErbB 3 , and c kit ) was examined in adult and developing rat taste papillae . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Overexpression of HER 2 / ErbB 2 , a homologue of the epidermal growth factor receptor , is associated with poor prognosis , and an ErbB 2 specific antibody is therapeutic when administered to patients with metastatic breast cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The transcriptional regulation of the human EGFR 3 and ERBB 2 genes has been extensively studied , particularly in the context of their overexpression in breast cancer . ^^^ We also describe novel therapies which may result from these studies and highlight directions for future research into the control of expression of the EGFR and ERBB 2 genes in the normal mammary gland and in breast cancer . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In line with this principle the expression of the epidermal growth factor receptor ( EGFR ) 3 and ErbB 2 receptors varies in the mammary gland during pregnancy , following the changing hormonal profile . ^^^ In breast cancer , expression of EGFR and ErbB 2 is clearly related to the absence of estrogen and progesterone receptors . ^^^ Moreover , transcriptional regulation of both EGFR and ERBB 2 by estrogens has been demonstrated . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
To model the development of neoplasia , particularly the preneoplastic changes caused by a single oncogene alone , several oncogenes have been expressed this way myc , Ha ras , erbB , erbB 2 , Wnt 1 , and hst / FGF 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 2 is a member of the ErbB / type 1 family of receptor tyrosine kinases which also includes epidermal growth factor receptor , ErbB 3 and ErbB 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Unique carboxyl terminal sequences of wild type and alternatively spliced variant forms of transforming growth factor alpha precursors mediate specific interactions with ErbB 4 and ErbB 2 . ^^^ We detected tyrosine phosphorylation of ErbB 2 in the absence of serum , in CHO cells expressing WT , VaI , or VaII , but not in mock transfectants . ^^^ WT co immunoprecipitated with ErbB 4 , but not with ErbB 1 , ErbB 2 , or ErbB 3 . ^^^ VaI and VaII co immunoprecipitated with ErbB 2 , but not with ErbB 1 , ErbB 3 , or ErbB 4 . ^^^ While interactions of WT and variant TGF alpha with the ErbBs all result in ErbB 2 activation , they produce different biological consequences , suggesting that the various TGF alpha precursors differentially modulate ErbB signaling . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We report the effect of heregulin beta 1 , the ligand for erbB 3 and erbB 4 receptors , on the regulation of vascular endothelial growth factor ( VEGF ) expression , using a panel of breast and lung cancer cell lines with constitutive erbB 2 overexpression or engineered to stably overexpress the erbB 2 receptor . ^^^ Overexpression of erbB 2 receptor results in induction of the basal level of VEGF and exposure to heregulin further enhances VEGF secretion . ^^^ In contrast , VEGF induction is significantly decreased in a T47D cell line where erbB 2 is functionally inactivated . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Western blot analysis showed activation of ErbB 2 and ErbB 3 , suggesting a possible mode of action of extracellular HRG in mammary gland carcinomas . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In 55 papillary carcinomas , increased cytoplasmic immunostaining of the ErbB 2 and ErbB 3 receptors was significantly associated with each other and with cytoplasmic epidermal growth factor receptor ( EGFR ) immunoreactivity , indicating a common regulatory mechanism . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
A pilot study on relationships of selected molecular factors [ erbB 1 , erbB 2 , erbB 3 , and c myc oncogene average gene copy numbers ( AGCN ) ; steroid receptors and pS 2 gene expression ; tumor cells ' DNA values ] to the ex vivo chemosensitivity of ovarian cancer in a modified adenosine triphosphate cell viability chemosensitivity assay ( ATP CVA ) , was performed . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The erbB 2 proto oncogene is overexpressed in approximately 30 % of breast cancers and is a major prognostic parameter when present in invasive disease . ^^^ A ligand for the erbB 2 receptor has not yet been identified but it can be activated by heterodimerization with heregulin ( HRG ) stimulated erbB 3 and erbB 4 receptors . ^^^ The erbB 3 and erbB 4 receptors are involved in transregulation of erbB 2 signaling . ^^^ HRG expressing breast cancer cell lines are characterized by low erbB receptor levels and a high invasive and metastatic index , while those which overexpress erbB 2 demonstrate minimal invasive potential in vitro and are non tumorigenic in vivo . ^^^ Addition of exogenous HRG to non invasive erbB 2 overexpressing cells ( SKBr 3 ) at low concentrations induced formation of pseudopodia , enhanced phagocytic activity and increased chemomigration and invasion in the Boyden chamber assay . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Stretch rapidly activated stress activated protein kinase 2 ( p 38 SAPK2 ) and Jun NH ( 2 ) terminal kinase ( JNK ) / SAPK pathways but not the Erk MAPK pathway and induced ErbB 2 but not ErbB 1 phosphorylation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Heregulin binds erbB receptors , and in our studies , primary cultures of both oligodendrocyte progenitor cells and differentiating oligodendrocytes expressed erbB 2 , erbB 3 , and erbB 4 receptors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Estrogen and progesterone facilitate erbB mediated glia to LHRH neuron communication by enhancing astrocytic gene expression of at least one of the EGF related ligands ( TGFalpha ) and two of the receptors ( erbB 2 and erbB 4 ) . ^^^ While Oct 2 transactivates the TGFalpha promoter , TTF 1 does so to the erbB 2 and LHRH genes but inhibits preproenkephalin promoter activity , suggesting that both transcriptional regulators may act coordinately in the normal hypothalamus to activate genes involved in facilitating the advent of puberty and repress those restraining sexual development . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
This pathway involves at least two distinct receptor kinases : EGF receptor ( ErbB 1 ) and ErbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In EGFR anti sense transfected cells , expression of erbB 3 , but not erbB 2 , was increased . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The erbB family of receptor tyrosine kinases , which consists of the epidermal growth factor receptor ( EGFr / erbB1 ) , erbB 2 ( neu ) , erbB 3 and erbB 4 , has been shown to be important for both normal development as well as neoplasia . ^^^ Elevations in EGFr and erbB 2 protein as well as erbB 2 : EGFr and erbB 2 : erbB 3 heterodimers were observed in skin of the erbB 2 transgenic mice . ^^^ Phosphotyrosine levels of the EGFr , erbB 2 and erbB 3 proteins were also elevated . ^^^ Constitutive expression of erbB 2 in epidermis of transgenic mice results in epidermal hyperproliferation and spontaneous skin tumor development . ^^^ The expression of rat erbB 2 was targeted to the basal layer of mouse epidermis with the bovine keratin 5 promoter . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We constructed chimeric proteins that contain in a single polypeptide chain a portion of human B 7 2 ( CD 86 ) genetically fused to single chain ( sc ) Fv antibody domains specific for the tumor associated antigens epidermal growth factor receptor and the closely related ErbB 2 receptor tyrosine kinase . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Of the investigated proto oncogenes ( Fos , Jun , ErbB 1 , ErbB 2 , Myc , Ras ) , only ErbB 2 is weakly associated with the in vitro short term test . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Ploidy , expression of erbB 1 , erbB 2 , P 53 and amplification of erbB 1 , erbB 2 and erbB 3 in non small cell lung cancer . ^^^ The aim of this study was to assess the prognostic value of deoxyribonucleic acid analysis , expression oferbB 1 , erbB 2 and P 53 , and amplification levels of erbB 1 , erbB 2 and erbB 3 in non small cell lung cancer ( NSCLC ) . ^^^ In another 108 cases , expression of erbB 1 , erbB 2 and P 53 was assessed immunhistochemically . ^^^ Of the tumours , 81 % were aneuploid and 14 % showed positive staining for erbB 1 , 18 % for erbB 2 and 41 % for P 53 . ^^^ There were normal mean gene copy numbers in 86 % for erbB 1 , 94 % for erbB 2 and in 96 % for erbB 3 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Sensitivity of mature Erbb 2 to geldanamycin is conferred by its kinase domain and is mediated by the chaperone protein Hsp 90 . ^^^ ErbB 2 is overexpressed in > 25 % of breast and ovarian cancers and is correlated with poor prognosis . ^^^ Although ErbB 2 and ErbB 1 are highly homologous , they respond quite differently to geldanamycin ( GA ) , an antibiotic that is a specific inhibitor of the chaperone protein Hsp 90 . ^^^ Thus , although both mature and nascent ErbB 2 proteins are down regulated by GA , only nascent ErbB 1 is sensitive to the drug . ^^^ To reveal the underlying mechanism behind these divergent responses , we made a chimeric receptor ( ErbB1 / 2 ) composed of the extracellular and transmembrane domains of ErbB 1 and the intracellular domain of ErbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Ethanol increased erbB 2 , erbB 3 , and erbB 4 expression in T47D human breast cancer cells in a concentration dependent manner . ^^^ Knocking out erbB 2 with an anti sense oligonucleotide eliminated heregulin beta 1 promoted migration and blocked ethanol induced chemo migration . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 2 , erbB 3 , and erbB 4 as well as neuregulin , agrin , and MuSK are known to be concentrated at the NMJ . ^^^ We have determined that erbB 2 and erbB 4 are enriched in the depths of the secondary junctional folds on the postsynaptic muscle membrane . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The aim of this study was to investigate if depletion of erbB 1 / EGFR and erbB 2 / HER2neu oncogene products by 17 allylamino 17 demethoxy Geldanamycin ( 17AAGA ) could diminish the metastatic potential of non small cell lung cancer ( NSCLC ) cells that express varying levels of the erbB1 / erbB2 oncogenes . ^^^ METHODS : NSCLC cell lines ( H 460 , H 358 , H 322 , or H 661 ) were assayed for expression of erbB 1 and erbB 2 , the cell adhesion molecule E cadherin , secretion of the matrix metalloproteinase 9 ( MMP 9 ) , and vascular endothelial cell growth factor ( VEGF ) , as well as their ability to invade Matrigel after 48 hour exposure to 17AAGA . ^^^ RESULTS : 17AAGA significantly depleted erbB 1 or erbB 2 levels in NSCLC cells expressing high levels of these proteins , and effectively inhibited their growth with IC 50 values ranging from 50 to 90 nmol / L . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The major partners of ErbB 2 in carcinomas are ErbB 1 ( also called EGFR ) and ErbB 3 , a kinase defective receptor whose potent mitogenic action is activated in the context of heterodimeric complexes . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
TCDD elevates erbB 2 expression and signaling in T47D cells by reversing serum potentiation of estrogen receptor activity , independent of estrogen levels and enhanced ER down regulation . 2 , 3 , 7 , 8 Tetrachlorodibenzo p dioxin ( TCDD ) induced erbB 2 and erbB 3 in estrogen receptor ( ER ) positive T47D ( T47D+ ) cells , but substantially slower than the direct induction of CYP1A1 or CYP1B1 . ^^^ TCDD enhanced heregulin stimulated signaling in T47D+ cells , in a parallel manner to erbB 2 and erbB 3 induction . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
AG 1478 and PD 153035 ( also know as AG 1517 ) have been adopted as specific ErbB 1 inhibitors based on their high specificity for ErbB 1 as compared to ErbB 2 in in vitro kinase assays . ^^^ In contrast , BIBX1382BS was more potent at inhibiting signaling induced by TGF alpha than that induced by neuregulin 1 beta1 or anti ErbB 2 agonist antibodies . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : To investigate the distribution and relative level of expression of the receptor tyrosine kinases , epidermal growth factor receptor ( EGFR ) , ErbB 2 and ErbB 3 , in human ocular surface epithelia . ^^^ METHODS : Immunofluorescent staining was performed to identify expression of the EGFR , ErbB 2 and ErbB 3 in the corneal , limbal and conjunctival epithelium in tissue sections and impression cytologies taken from normal human eyes . ^^^ RESULTS : The three receptor tyrosine kinases , EGFR , ErbB 2 and ErbB 3 , were detected in human corneal , limbal and conjunctival epithelia by immunofluorescent staining . ^^^ CONCLUSION : EGFR , ErbB 2 and ErbB 3 are expressed by the ocular surface epithelia . ^^^ Expression of the receptor tyrosine kinases , epidermal growth factor receptor , ErbB 2 , and ErbB 3 , in human ocular surface epithelia . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Down regulation of ErbB receptor activity , through the use of specific pharmacological inhibitors or dominant negative receptor constructs , revealed that IL 6 induced MAPK activation was largely dependent on epidermal growth factor ( EGF ) receptor activity , but not on ErbB 2 activity . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
One of these receptors , HER2 / neu , or ErbB 2 , is the target for a new rational therapeutic antibody , Herceptin . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The network is often dysregulated in cancer and lends credence to the mantra that molecular understanding yields clinical benefit : over 25 , 000 women with breast cancer have now been treated with trastuzumab ( Herceptin ) , a recombinant antibody designed to block the receptor ErbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Our recent studies indicate that ErbB 4 interacts with postsynaptic density ( PSD ) 95 ( SAP 90 ) , a PDZ domain containing protein that does not interact with ErbB 2 or ErbB 3 . ^^^ Using as bait the ErbB 2 C terminus , we identified Erbin , another PDZ domain containing protein that interacts specifically with ErbB 2 . ^^^ Erbin is concentrated in postsynaptic membranes at the neuromuscular junction and in the central nervous system , where ErbB 2 is concentrated . ^^^ Expression of Erbin increases the amount of ErbB 2 labeled by biotin in transfected cells , suggesting that Erbin is able to increase ErbB 2 surface expression . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The ErbB family of receptors , which includes the epidermal growth factor receptor ( EGFR ) , ErbB 2 , ErbB 3 , and ErbB 4 , mediate signaling by EGF like polypeptides . ^^^ EGF was found to activate the pro survival protein kinase Akt in stable cell lines expressing K721M and ErbB 2 but , unlike cells expressing wild type EGFR , was incapable of activating signal transducers and activators of transcription ( STAT ) or driving cell proliferation . ^^^ These results demonstrate that EGFR ErbB 2 oligomers are potent activators of MAPK and Akt , and this signaling does not require EGFR kinase activity . . ^^^ K721M alone exhibited no detectable signaling capacity , whereas coexpression of K721M with ErbB 2 , but not ErbB 3 or ErbB 4 , resulted in EGF dependent mitogen activated protein kinase ( MAPK ) activation . ^^^ The kinase activity , but not tyrosine phosphorylation , of ErbB 2 was required for EGF induced MAPK activation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The present study showed that erbB 2 , erbB 3 , and erbB 4 transcripts and protein are distributed throughout all areas of adult rat brain . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Previously , we documented the expression of type 1 growth factor receptors [ ERBB1 / EGFR ( epidermal growth factor receptor ) , ERBB 2 , ERBB 3 and ERBB 4 ] in the full range of cervical neoplasias by immunohistochemistry assay . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In order to study the association of histological grade ( HG ) with specific clinical and biological parameters which may influence the clinical behavior of infiltrating ductal carcinomas of the breast ( IDC ) , we analyzed in 229 tissue samples the cytosolic concentrations of estrogen receptor ( ER ) , progesterone receptor ( PR ) , pS 2 , cathepsin D , hyaluronic acid ( HA ) and tissue type plasminogen activator ( t PA ) , as well as those of the erbB 2 oncoprotein , epidermal growth factor receptor ( EGFR ) , HA , CD44v5 and CD44v6 in the cell membrane fraction . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Mice heterozygous ( + / ) for either heregulin ( HRG ) , ErbB 2 , or ErbB 3 were created by gene targeting , resulting in the loss of one functional gene copy and an associated decrease in targeted protein . ^^^ However , pregnant WT mice and ErbB 2 and ErbB 3 heterozygous mice treated with rHRG beta 1 were less affected , with significantly lower mortality rates and a less severe abdominal phenotype . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The fatty acid enhanced the tyrosine phosphorylation of ErbB 4 but not of ErbB 2 or ErbB 3 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
These effects were specific for an EGFR mediated pathway because cotreatment with AG 825 , an erbB 2 inhibitor , had little effect on apoptosis . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Treatment of cells with EGF ( ErbB 1 specific ) or heregulin ( ErbB 4 specific ) resulted in a hierarchic transactivations of ErbB 2 and ErbB 3 dependent on GF binding specificity . ^^^ Downstream consequences of these ErbB interactions were examined with MAPK after specifically inhibiting ErbB 1 ( or 4 ) with tyrphostin AG 1478 or ErbB 2 with tyrphostin AG 825 . ^^^ Inhibiting ErbB 2 caused an enhanced MAPK response simulating an amplified ErbB 1 ( or 4 ) response . ^^^ Thus ErbB 2 is a modulator of ErbB 1 ( or 4 ) function leading to different MAPK response profiles to GF or radiation exposure . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Analysis of 65 ErbB 2 expressing primary breast cancers reveals a highly significant relationship between Ser 1113 phosphorylation and EGFR overexpression ( p < 0 . 0001 ) as well as an association with poor prognosis ( p = 0 . 005 ) . ^^^ Association of ErbB 2 Ser1113 phosphorylation with epidermal growth factor receptor co expression and poor prognosis in human breast cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The number of EGFR molecules was increased in cells overexpressing [ K44A ] dynamin , while the number of proto oncoprotein ErbB 2 molecules was unaltered . ^^^ ErbB 2 EGFR heterodimer formation was found to be ligand independent , and the number of heterodimers was not altered by overexpression of [ K44A ] dynamin . ^^^ Furthermore , the EGF induced tyrosine phosphorylation of ErbB 2 was not affected by overexpression of [ K44A ] dynamin , implying that EGFR ErbB 2 dimers were fully functional . ^^^ Our results strongly suggest that high affinity binding of EGF and EGFR ErbB 2 heterodimerization are regulated by different mechanisms . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Despite the expression of erbB 2 mRNA , the trophectoderm was devoid of immunoreactive ErbB 2 . ^^^ At the site of implantation , uterine luminal epithelial cells apposing the preimplantation blastocyst displayed a distinct membrane immunolocalization of ErbB 2 , identifying the uterine epithelium as target for EGF , TGFalpha , and HB EGF derived from both the embryonic trophectoderm and the uterine epithelium . ^^^ The detection of tyrosine phosphorylated ErbB 2 in the rabbit placenta indicated the presence of a functional ErbB / EGF like system in the pregnant rabbit uterus . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
A naturally occurring secreted human ErbB 3 receptor isoform inhibits heregulin stimulated activation of ErbB 2 , ErbB 3 , and ErbB 4 . ^^^ In this study , we demonstrate that a naturally occurring secreted form of the human ErbB 3 receptor , p 85 soluble ErbB 3 ( sErbB 3 ) , is a potent negative regulator of heregulin ( HRG ) stimulated ErbB 2 , ErbB 3 , and ErbB 4 activation . ^^^ We show that p 85 sErbB3 binds to HRG with an affinity comparable to that of full length ErbB 3 and competitively inhibits high affinity HRG binding to ErbB2 / ErbB3 heterodimers on the cell surface of breast carcinoma cells with an IC ( 50 ) of 0 . 5 nM . p 85 sErbB3 inhibits HRG induced phosphorylation of ErbB 2 , ErbB 3 , and ErbB 4 in breast carcinoma derived cell lines and can also block HRG stimulated activation of mitogen activated protein kinase , Akt , and association of ErbB 3 with the phosphatidylinositol 3 ' kinase p 85 regulatory subunit . ^^^ The IC ( 50 ) for both p 85 sErbB3 and 2C4 ( a monoclonal antibody specific for ErbB 2 ) mediated inhibition of HRG binding is approximately 0 . 5 nM , although the mechanism of inhibition by these two proteins is distinct . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Signal therapy for RAS induced cancers in combination of AG 879 and PP 1 , specific inhibitors for ErbB 2 and Src family kinases , that block PAK activation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We show here that embryonic striatal NPs express multiple Nrg 1 transcripts and proteins as well as their specific receptors , ErbB 2 and ErbB 4 , but not ErbB 3 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Human carcinomas frequently express high levels of receptors in the EGF receptor family , and overexpression of at least two of these receptors , the EGF receptor ( EGFr ) and closely related ErbB 2 , has been associated with a more aggressive clinical behavior . ^^^ In the last two decades monoclonal antibodies ( MAbs ) which block activation of the EGFr and ErbB 2 have been developed . ^^^ Clinical activity with these antibodies has been documented : trastuzumab , a humanized anti ErbB 2 MAb , is active and was recently approved in combination with paclitaxel for the therapy of patients with metastatic ErbB 2 overexpressing breast cancer ; IMC C 225 , a chimeric anti EGFr MAb , has shown impressive activity when combined with radiation therapy and reverses resistance to chemotherapy . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : erbB 2 and epidermal growth factor receptor ( EGFR ) may mediate motility via signaling that enables changes in the actin cytoskeleton . ^^^ EXPERIMENTAL DESIGN : The expression of erbB 2 , EGFR , and gelsolin was analyzed in 790 archival invasive breast cancers . ^^^ Tumor gelsolin was associated with overexpression of erbB 2 and EGFR , as well as with an aggressive tumor phenotype . ^^^ Gelsolin as a negative prognostic factor and effector of motility in erbB 2 positive epidermal growth factor receptor positive breast cancers . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The expression of erbB 2 and epidermal growth factor receptor ( EGFR ) in colorectal cancers has been suggested to have diagnostic and prognostic significance . ^^^ The presence of the 10 allele of ER gene significantly correlated with the overexpression of the erbB 2 and EGFR oncogenes . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
HER 2 ( neu , erbB 2 ) , a receptor related to the human epidermal growth factor receptor , has now become more important as a predictive marker of treatment response . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Expression of individual EGF receptor ( EGFR ) and ErbB 2 , ErbB 3 , or ErbB 4 receptors was detected in 72 . 2 , 44 . 5 , 56 . 3 , and 29 . 8 % of bladder cancer cases , respectively . ^^^ Important indicators in association with patient survival were tumor staging ( P = 0 . 017 ) , ErbB 2 ( P = 0 . 018 ) , EGFR ErbB 2 ( P = 0 . 023 ) , and ErbB 2 ErbB3 ( P = 0 . 042 ) . ^^^ In the subset of grade 2 tumors , EGFR ErbB 2 ErbB3 and EGFR ErbB 2 predicted the development of second recurrence ( P = 0 . 026 and 0 . 039 , respectively ) , and ErbB 2 ErbB3 tended to correlate with patient survival ( P = 0 . 09 ) . ^^^ The results indicate that a combination of EGFR , ErbB 2 , and ErbB 3 expression profile may be a better prognostic indicator than any family member alone . ^^^ Given that ErbB 2 is the preferred coexpression partner of ErbB family members , expression of other ErbB receptors may significantly affect the prognostic implication of ErbB 2 for bladder cancer patients . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The compounds were evaluated for their inhibition of phosphorylation of the isolated EGFR enzyme and for inhibition of EGF stimulated autophosphorylation of EGFR in A 431 cells and of heregulin stimulated autophosphorylation of erbB 2 in MDA MB 453 cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In contrast , the phenotypes of transgenic mice expressing dominant negative ERBB 2 and ERBB 4 proteins suggest that these receptors differentially act to promote or maintain alveolar differentiation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
It is well established that ErbB 1 and ErbB 2 can cooperate in mammary epithelial cell transformation . ^^^ Therefore , to understand how ErbB1 / ErbB2 signaling contributes to this process , we used the ErbB kinase inhibitor AG1478in ErbB 2 dependent BT 474 and SKBR 3 human breast cancer cells . ^^^ These cells overexpress ErbB 2 and also display moderate levels of ErbB 1 . ^^^ Treatment with AG 1478 resulted in rapid ErbB 2 dephosphorylation , reversible G ( 1 ) arrest , and interruption of constitutive mitogen activated protein kinase ( MAPK ) and phosphatidylinositol 3 kinase ( PI3K ) / Akt signaling . ^^^ These data imply that : ( a ) modulation of both p 27 and cyclin D 1 are required for the growth arrest that results from blockade of the ErbB 2 kinase ; and ( b ) ErbB 2 overexpressing cells use both MAPK and PI3K / Akt to modulate p 27 and cyclin D 1 and , hence , subvert the G ( 1 ) to S transition . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 2 , but not ErbB 1 , reinitiates proliferation and induces luminal repopulation in epithelial acini . ^^^ Both ErbB 1 and ErbB 2 are overexpressed or amplified in breast tumours . ^^^ To examine the effects of activating ErbB receptors in a context that mimics polarized epithelial cells in vivo , we activated ErbB 1 and ErbB 2 homodimers in preformed , growth arrested mammary acini cultured in three dimensional basement membrane gels . ^^^ Activation of ErbB 2 , but not that of ErbB 1 , led to a reinitiation of cell proliferation and altered the properties of mammary acinar structures . ^^^ ErbB 2 activation also disrupted tight junctions and the cell polarity of polarized epithelia , whereas ErbB 1 activation did not have any effect . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : Expression of ErbB 1 and ErbB 2 ( epidermal growth factor receptor and HER2 / neu ) in breast cancer may cause tamoxifen resistance , but not all studies concur . ^^^ Letrozole is more effective neoadjuvant endocrine therapy than tamoxifen for ErbB 1 and / or ErbB 2 positive , estrogen receptor positive primary breast cancer : evidence from a phase 3 randomized trial . ^^^ Additionally , the relationship between ErbB 1 and ErbB 2 expression and response to selective aromatase inhibitors is unknown . ^^^ ErbB 1 and ErbB 2 IHC were assessed by intensity and completeness of membranous staining according to published criteria . ^^^ Differences in response rates between letrozole and tamoxifen were most marked for tumors that were positive for ErbB 1 and / or ErbB 2 and ER ( 88 % 5 21 % , P = . 0004 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Use of ErbB 1 and ErbB 2 to select endocrine therapy for breast cancer : will it play in Peoria . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Human skin , cultured normal keratinocytes , and A 431 skin carcinoma cells expressed ErbB 1 , ErbB 2 , and ErbB 3 , but not ErbB 4 . ^^^ Despite strong expression of ErbB 2 and ErbB 3 , heregulin was inactive in stimulating tyrosine phosphorylation in A 431 cells . ^^^ ErbB 2 displayed punctate cytoplasmic staining in A 431 and keratinocytes , compared to strong cell surface staining in MDA MB 453 . ^^^ In skin , ErbB 2 was cytoplasmic in basal keratinocytes , assuming a cell surface pattern in the upper suprabasal layers . ^^^ These results suggest that in skin keratinocytes , ErbB 2 transduces ligand dependent differentiation signals , whereas ErbB 1 transduces ligand dependent proliferation / survival signals . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The erbB 2 gene is required for the development of terminally differentiated spinal cord oligodendrocytes . ^^^ Here , we show that erbB 2 is not necessary for the early stages of oligodendrocyte precursor development , but is essential for proligodendroblasts to differentiate into galactosylcerebroside positive ( GalC+ ) oligodendrocytes . ^^^ In the presence of erbB 2 , oligodendrocyte development is normal . ^^^ In the absence of erbB 2 ( erbB 2 / ) , however , oligodendrocyte development is halted at the proligodendroblast stage with a > 10 fold reduction in the number of GalC+ oligodendrocytes . ^^^ ErbB 2 appears to function in the transition of proligodendroblast to oligodendrocyte by transducing a terminal differentiation signal , since there is no evidence of increased oligodendrocyte death in the absence of erbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Among the ErbB receptors only ErbB 2 has no direct ligand ; however , ErbB 2 acts as a co receptor for the other family members , promoting high affinity ligand binding and enhancement of ligand induced biological responses . ^^^ These characteristics demonstrate the central role of ErbB 2 in the receptor family , which likely explains why it is involved in the development of many human malignancies , including breast cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
To determine whether MEC and ACC have different molecular characteristics , we examined the expression of erbB 2 , erbB 3 , epidermal growth factor receptor ( EGFR ) , and transforming growth factor alpha ( TGF alpha ) , important molecular features in other malignancies . ^^^ Conversely , erbB 2 , erbB 3 , EGFR , and TGF alpha may have a role in the development and progression of MEC . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The characterization of novel , dual ErbB 2 / EGFR , tyrosine kinase inhibitors : potential therapy for cancer . ^^^ The best characterized of these proteins are the epidermal growth factor receptor ( EGFR ) and ErbB 2 ( HER 2 / neu ) . ^^^ We have developed potent quinazoline and pyrido [ 3 , 4 d ] pyrimidine small molecules that are dual inhibitors of ErbB 2 and EGFR . ^^^ The compounds demonstrate potent in vitro inhibition of the ErbB 2 and EGFR kinase domains with IC ( 50 ) s < 80 nM . ^^^ Growth of ErbB 2 and EGFR expressing tumor cell lines is inhibited at concentrations < 0 . 5 microM . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Unlike previous synergies demonstrated between ErbB 2 blockade and DNA damaging drugs , the synergy between the irreversible EGFR inhibitor and cisplatin does not appear to involve the repair of DNA cisplatin adducts . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Here , we tested whether CD 44 interacts with erbB 2 and another type 1 receptor , the epidermal growth factor receptor ( EGFR ) , in human cervical carcinoma tissues and cell lines and whether these interactions influence erbB 2 signaling . ^^^ METHODS : CD 44 , EGFR , and erbB 2 colocalization were examined in 36 pT1b pT2b cervical cancer cases and in the CaSki and SiHa cervical carcinoma cell lines by immunohistochemistry and laser scanning confocal microscopy . ^^^ The role of CD 44 EGFR erbB 2 interactions in erbB 2 signaling was examined by immunoprecipitation and using antisense CD 44 oligonucleotides . ^^^ RESULTS : CD 44 , erbB 2 , and EGFR coexpression and colocalization were observed in 42 % ( 15 / 36 ) of cervical carcinoma cases and in both cervical carcinoma cell lines . ^^^ CD 44 coimmunoprecipitated with erbB 2 and EGFR in cervical carcinoma cell lysates , indicating that these proteins interact with each other . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PKI 166 , a pyrrolo [ 2 , 3 , d ] pyrimidine derivative , is a dual inhibitor of both the EGFR and the ErbB 2 kinases . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The length of RT PCR products were 380 bp for erbB 1 , 500 bp for erbB 2 , 644 bp for erbB 3 , and 416 bp for erbB 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Truncated ErbB 2 receptor enhances ErbB 1 signaling and induces reversible , ERK independent loss of epithelial morphology . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Mechanisms of ErbB 2 mediated paclitaxel resistance and trastuzumab mediated paclitaxel sensitization in ErbB 2 overexpressing breast cancers . ^^^ The ErbB 2 gene encodes a transmembrane growth factor receptor that belongs to the ErbB receptor tyrosine kinase subfamily . ^^^ ErbB 2 protein is overexpressed in approximately 30 % of breast cancers . ^^^ Although controversies exist , data from our laboratory and from clinical trials of trastuzumab indicate that ErbB 2 overexpression confers chemoresistance to certain chemotherapeutic agents such as paclitaxel . ^^^ One of the molecular mechanisms of ErbB 2 mediated paclitaxel resistance is that overexpression of the ErbB 2 receptor leads to deregulation of the G2 / M cell cycle check point that inhibits paclitaxel induced apoptosis . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
This inhibition is highly selective for erbB 1 ( epidermal growth factor receptor ) , erbB 2 , erbB 3 , and erbB 4 without inhibiting tyrosine kinase activity of receptors such as platelet derived growth factor receptor , fibroblast growth factor receptor , and insulin receptor , even at high concentrations . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Spectral changes induced by the Val > Glu mutation in ErbB 1 were smaller than those induced by the analogous oncogenic mutation in the homologous human receptor , ErbB 2 ( Sharpe , S . , K . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Here we show that the activation of PPARgamma through the 15 deoxy Delta 12 , 14 prostaglandin J ( 2 ) ( PG J ( 2 ) ) ligand causes a dramatic inhibition of ErbB 2 and ErbB 3 tyrosine phosphorylation caused by neuregulin 1 ( NRG 1 ) and neuregulin 2 ( NRG 2 ) in MCF 7 cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Among invasive and in situ carcinoma , EGFR expression was the most prevalent ( in 29 / 32 and 8 / 11 cases , respectively ) followed by ErbB 2 ( 17 / 32 and 2 / 11 ) and ErbB 4 ( 9 / 32 and 1 / 10 ) , while ErbB 3 was only detected in invasive tumours ( 12 / 32 ) . ^^^ Some benign lesions and histologically normal mucosa adjacent to carcinomas showed weak immunostaining of EGFR ( 10 / 28 ) , ErbB 2 ( 4 / 28 ) or ErbB 4 ( 3 / 28 ) . ^^^ By comparison , overexpression , as indicated by increased staining intensity , was observed in invasive tumours for EGFR ( 18 / 32 ) , ErbB 2 ( 8 / 32 ) , ErbB 4 ( 3 / 32 ) , and ErbB 3 ( 3 / 32 ) . ^^^ Statistical evaluation demonstrated a significant association of EGFR or ErbB 2 overexpression with invasive carcinoma when compared with benign lesions and apparently normal epithelium ( p=5 . 2x10 ( 7 ) and p=5x10 ( 3 ) , respectively ) . ^^^ Tumour specific overexpression of ErbB receptors and their co expression , most frequently involving EGFR and ErbB 2 , in the same cell layer of neoplastic epithelium , implicate receptor heterodimers in the pathogenesis of oral squamous carcinoma . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
RESULTS : The expression profiles demonstrated varying levels of EGFR , ErbB 2 , ErbB 3 , and ErbB 4 expression . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Specifically , ligand dependent ErbB 2 transactivation requires a discrete three amino acid segment , located at the C terminus of ErbB family members ErbB 3 , ErbB 4 , and the epidermal growth factor receptor . ^^^ Structural requirements for ErbB 2 transactivation . ^^^ ErbB 2 is a unique member of the ErbB family of receptor tyrosine kinases that is distinguished by the fact that no ligand has yet been identified . ^^^ Due to the absence of an ErbB 2 ligand , alternative mechanisms are used for ErbB 2 activation . ^^^ As such , when ErbB 2 is overexpressed , kinase activation occurs in the absence of ligand because of constitutive homodimerization . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Erk 5 participates in neuregulin signal transduction and is constitutively active in breast cancer cells overexpressing ErbB 2 . ^^^ Activation of ErbB1 / EGFR is mainly triggered by epidermal growth factor ( EGF ) and other related ligands , while activation of ErbB 2 , ErbB 3 , and ErbB 4 receptors occurs by binding to another set of EGF like ligands termed neuregulins ( NRGs ) . ^^^ Analysis of Erk 5 in several human tumor cell lines indicated that a constitutively active form of this kinase was present in the BT 474 and SKBR 3 cell lines , which also expressed activated forms of ErbB 2 , ErbB 3 , and ErbB 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Using an approach for analyzing TM domain interactions in Escherichia coli cell membranes , named TOXCAT , we find that the TM domains of ErbB receptors self associate strongly in the absence of their extracellular domains , with the rank order ErbB 4 TM > ErbB 1 TM equivalent to ErbB 2 TM > ErbB 3 TM . ^^^ We also analyzed the effect of the valine to glutamic acid mutation in ErbB 2 that constitutively activates this receptor . ^^^ Contrary to our expectations , this mutation reduced rather than increased ErbB 2 TM dimerization . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ZD 1839 ( Iressa ) , a novel epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor , potently inhibits the growth of EGFR positive cancer cell lines with or without erbB 2 overexpression . ^^^ Overexpression of the growth factor receptors EGFR and erbB 2 occurs frequently in several human cancers and is associated with aggressive tumour behaviour and poor patient prognosis . ^^^ We have investigated the effects of ZD 1839 ( Iressa ) , a novel EGFR tyrosine kinase inhibitor , on the growth , in vitro and in vivo , of human cancer cell lines expressing various levels of EGFR and erbB 2 . ^^^ It also inhibited proliferation in EGFR ( + ) cancer cell lines overexpressing erbB 2 ( SKBr 3 , SKOV 3 , BT 474 ) by between 20 % and 80 % , effects which correlated with inhibition of EGF dependent erbB 2 phosphorylation and activation of ERK MAP kinase and PKB / Akt in SKOV 3 cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Epidermal growth factor receptor ( HER 1 ) tyrosine kinase inhibitor ZD 1839 ( Iressa ) inhibits HER2 / neu ( erbB 2 ) overexpressing breast cancer cells in vitro and in vivo . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
OBJECTIVE : To evaluate the expression of type 1 growth factor receptor family [ epidermal growth factor receptor ( EGFR ) , ErbB 2 and ErbB 3 ] by the epithelium in pterygium so as to understand the pathogenesis of this disorder . ^^^ METHODS : The immunofluorescent staining and Western blotting were performed in 15 patients with primary pterygium , compared to normal conjunctival epithelium , to determine the expression of EGFR , ErbB 2 and ErbB 3 proteins . ^^^ RESULTS : The EGFR was present at the basal cells while the ErbB 2 and ErbB 3 were expressed by the superficial cells in normal conjunctival epithelium in immunofluorescent staining . ^^^ Of 15 pterygia , 11 pterygia expressed the stains of EGFR , ErbB 2 and ErbB 3 in the full thickness of epithelium and with stronger staining compared to the control group , 4 of them showed the same staining pattern as that in the normal conjunctiva . ^^^ Compared to normal conjunctiva , the stronger density of protein bands of EGFR , ErbB 2 and ErbB 3 was also demonstrated by western blotting in 11 pterygia with strong staining of these antibodies . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Transactivation of ErbB 2 and ErbB 3 by tumor necrosis factor alpha and anisomycin leads to impaired insulin signaling through serine / threonine phosphorylation of IRS proteins . ^^^ Specific inhibitors of the ErbB 2 tyrosine kinase abrogated the activation of ErbB2 / ErbB3 and in parallel prevented the reduction in IRS protein functions . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Of the proto oncogenes and suppressor gene products N RAS , P 53 , FOS and JUN revealed a relationship to the take rate of NSCLC , while such a relationship was not found with MYC , ERBB 1 and ERBB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
EGFR and ErbB 2 differentially regulate Raf 1 translocation and activation . ^^^ In SKBR 3 breast cancer cells , which express high levels of EGFR and ErbB 2 , treatment with EGF also resulted in rapid accumulation of EGFR and Raf 1 into endocytotic vesicles , but EGFR endocytosis was inhibited and Raf 1 remained associated with the plasma membrane for a prolonged period . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The tumour antigen ErbB 2 belongs to the epidermal growth factor receptor family . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Grb 7 is an adapter type signaling protein , which is recruited via its SH 2 domain to a variety of receptor tyrosine kinases ( RTKs ) , including ErbB 2 and ErbB 3 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
One receptor that has been found to play a central role in this signaling network is ErbB 2 / Neu , and it is considered the preferred heterodimerization partner for other members of the EGFR family . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
BACKGROUND : Co expression of the epidermal growth factor receptor ( EGFR ) and of ErbB 2 is found in a subset of primary human breast cancer . ^^^ MATERIALS AND METHODS : The antiproliferative effects of anti EGFR and anti ErbB 2 agents were evaluated using a monolayer assay . ^^^ The effects of these agents on the activation of EGFR , ErbB 2 , AKT and p42 / p44 MAP kinases ( MAPK ) were investigated by western blot analysis . ^^^ RESULTS : We found that both ZD 1839 ( Iressa ) , a specific EGFR tyrosine kinase inhibitor , and trastuzumab ( Herceptin ) ( TRA ) , a humanized anti ErbB 2 monoclonal antibody , were able to inhibit the growth of SK Br 3 and BT 474 breast carcinoma cells , which express both EGFR and ErbB 2 . ^^^ Treatment of SK Br 3 cells with ZD 1839 produced a significant , dose dependent reduction of the tyrosine phosphorylation of both EGFR and ErbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Nrdp 1 interacts specifically with the neuregulin receptors ErbB 3 and ErbB 4 and not with epidermal growth factor receptor or ErbB 2 . ^^^ When coexpressed in COS 7 cells , Nrdp 1 mediates the redistribution of ErbB 3 from the cell surface to intracellular compartments and induces the suppression of ErbB 3 and ErbB 4 receptor levels but not epidermal growth factor receptor or ErbB 2 levels . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Cathepsin D , pS 2 , neuron specific enolase ( NSE ) and CA 125 cytosolic concentrations were determined , as well as those of epidermal growth factor receptor ( EGFR ) , erbB 2 protein , CD44s , CD44v5 and CD44v6 on cell surface membranes . ^^^ In squamous carcinomas , pS 2 positivity was associated with lower EGFR ( p : 0 . 02270 ) levels and higher erbB 2 protein ( p : 0 , 00563 ) concentrations . ^^^ Conclusions : Our results led us to suggest the following : 1 ) cytosolic pS 2 concentrations are higher in tumoral than in normal samples ; 2 ) adenoarcinomas had higher levels than squamous lung carcinomas ; 3 ) in adenocarcinomas , positivity for pS 2 is associated with lower EGFR levels and higher CA 125 concentrations suggesting a worse outcome , and 4 ) in squamous lung tumors , positivity for pS 2 was associated with lower EGFR and higher erbB 2 oncoprotein concentrations , it not being possible to establish its clinical significance , although it may be correlated with a poor prognosis . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Further immunohistochemical analysis showed that tumors that overexpressed both epidermal growth factor receptor ( EGFR ) and erbB 2 had higher levels of cox 2 and laminin 5 than those without concomitant overexpression of these proteins ( P = 0 . 014 and P = 0 . 018 , respectively ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Herstatin is an autoinhibitor of the ErbB family consisting of subdomains 1 and 2 of the human epidermal growth factor receptor 2 ( ErbB 2 ) extracellular domain and a novel C terminal domain encoded by an intron . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
For example , unique high levels of expressions were found for the HLH protein ID 1 ( MCF 7 ) and the receptor tyrosine kinase erbB 2 ( SK BR 3 and T 47D ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
CD 44 associates with EGFR and erbB 2 in metastasizing mammary carcinoma cells . ^^^ Type 1 receptor tyrosine kinases , including the epidermal growth factor receptor ( EGFR ) and erbB 2 , have been implicated in mammary carcinoma growth and metastasis . ^^^ Here , the authors tested whether CD 44 , EGFR , and erbB 2 interacted and colocalized with one another in four mammary carcinoma cell lines ( MCF 7 , MDA MB 231 , MDA MB 435 , and MDA MB 436 ) and in cytology samples obtained from patients with metastatic breast cancer . ^^^ CD 44 constitutively colocalized and coimmunoprecipitated with erbB 2 and EGFR in all four mammary carcinoma cell lines . ^^^ CD 44 also colocalized with erbB 2 and EGFR in all cytology samples expressing erbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : This study was conducted to evaluate the clinical significance of the localization of epidermal growth factor receptor ( EGF r ) , transforming growth factor ( TGF ) alpha , and erbB 2 in the development , progression and prognosis of squamous cell cancers ( SCCs ) of the lung . ^^^ EXPERIMENTAL DESIGN : The localization of EGF r , TGF alpha , and erbB 2 was evaluated immunohistochemically in 60 archival specimens of SCC of the lung and in 60 lung specimens without cancer . ^^^ RESULTS AND CONCLUSIONS : The expression of EGF r , erbB 2 , and TGF alpha were significantly higher in SCC and associated precancerous lesions than in the normal bronchial epithelium and hyperplastic lesions of noncancer specimens . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In breast tumors , expression of epidermal growth factor receptor ( EGFR ) and / or erbB 2 is associated with poor prognosis ; the therapeutic utility of blocking these receptors has been established using trastuzumab ( Herceptin ) , a monoclonal antibody that blocks erbB 2 signaling . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We have examined whether signaling by HER2 / neu ( erbB 2 ) receptor tyrosine kinase , which can induce antiestrogen resistance , can also disrupt the tamoxifen induced interaction of ER with transcriptional corepressors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Modulation of p 53 , ErbB 1 , ErbB 2 , and Raf 1 expression in lung cancer cells by depsipeptide FR 901228 . ^^^ Western blot and immunoprecipitation techniques were used to analyze expression of cell cycle proteins ( cyclin A , cyclin E , p 53 , and p 21 ) , signaling related proteins ( ErbB 1 , ErbB 2 , and Raf 1 ) , activity of extracellular signal regulated kinase 1 and 2 ( ERK1 / 2 ) , binding of mutant p 53 and Raf 1 to heat shock protein ( Hsp ) 90 , and acetylation of Hsp 90 . ^^^ FK 228 treated cells also were depleted of ErbB 1 , ErbB 2 , and Raf 1 proteins , and exhibited lower ERK1 / 2 activity . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
OBJECTIVE : To evaluate the expression of the type 1 growth factor receptor family [ epidermal growth factor receptor ( EGFR ) , ErbB 2 and ErbB 3 ] by the epithelial cells in pterygium . ^^^ METHODS : Immunoflourescent staining and Western blotting were performed to detect the expression pattern and quantity of EGFR , ErbB 2 and ErbB 3 proteins in the epithelia of 15 patients with primary pterygium and 12 subjects with normal conjunctiva . ^^^ RESULTS : In immunofluorescent staining , the EGFR protein was present in the basal cells while the ErbB 2 and ErbB 3 were expressed by the superficial cells in normal conjunctival epithelium . ^^^ Of the pterygium cases 15 , 11 were stained by EGFR , ErbB 2 and ErbB 3 in the full thickness of the epithelium and showed stronger staining compared with the control group . ^^^ Compared with normal conjunctiva , stronger protein bands of these three receptors were found in all of the pterygium specimens , in which EGFR , ErbB 2 and ErbB 3 were expressed in the full thickness , as shown by immunofluorescent staining . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Constitutively activated Stat 3 alpha is often correlated with the activation of ErbB 2 , a member of the EGFR family . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : Several genes are reported to be implicated in bladder carcinogenesis , including p 53 , p16INK4a , pRb , erbB 2 , Cyclin D 1 , H ras , EGFR , and c myc . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Here we show that treatment of A 431 cells with different epidermal growth factor receptor ligands can cause growth inhibition to an extent paralleling ErbB 2 tyrosine phosphorylation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Particularly , the interactions among ErbB 1 and ErbB 2 or ErbB 4 and ErbB 2 are known to be involved in the stimulation of LHRH secretion during sexual maturation . ^^^ Disruption of functional ErbB 4 / 2 receptor complex by blocking ErbB 2 receptor synthesis in the hypothalamus via an infusion of ErbB 2 antisense oligodeoxynucleotide resulted in an estrous acyclicity in young adult rats . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Ligand independent ErbB 2 activation occurs principally by two distinct mechanisms : overexpression and mutation . ^^^ Overexpression of ErbB 2 at the plasma membrane drives receptor self association in a concentration dependent manner , which in turn leads to constitutive receptor activation . ^^^ Subsets of human breast cancers contain a molecular alteration that leads to erbB 2 gene amplification and subsequent protein overexpression . ^^^ Although not recognized to occur in human cancers , mutation can also lead to increased ErbB 2 association . ^^^ In each case , a number of explanations have been proposed to explain the resulting ErbB 2 activation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The expression of erbB 2 , epidermal growth factor receptor ( EGFR ) , p 53 , and ras in colorectal cancer has been suggested to have diagnostic and prognostic significance . ^^^ PATIENTS AND METHODS : We investigated the relationship between the CaSR A986S polymorphism and the expression of erbB 2 , EGFR , p 53 , and ras as well as the UICC stage in 56 patients with rectal cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Interaction between ErbB 1 and ErbB 2 transmembrane domains in bilayer membranes . ^^^ ErbB 2 , which has not been observed to form active homo dimers in a ligand dependent manner , has been implicated as an important partner for formation of hetero dimers with other ErbB receptors . ^^^ Recent work has shown that the ErbB 2 transmembrane domain is capable of forming homo oligomeric species in lipid bilayers , while a similar domain from ErbB 1 appears to have a lesser tendency to such interactions . ^^^ Here , 2H nuclear magnetic resonance was used to investigate the role of the ErbB 2 transmembrane domain in hetero oligomerisation with that of ErbB 1 . ^^^ At low total concentrations of peptide in the membrane , ErbB 2 transmembrane domains were found to decrease the mobility of corresponding ErbB 1 domains . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 2 activation of ESX gene expression . ^^^ In cell lines and in 45 primary ductal breast cancers we show that ESX transcript expression significantly correlates with ErbB 2 transcript levels . ^^^ Moreover , expression of ErbB 2 in cells upregulates ESX promoter activity while inhibition of ErbB 2 or its downstream signaling pathways decrease both ESX promoter activity and endogenous ESX protein levels . ^^^ These results indicate that the ESX promoter represents a transcriptional target of ErbB 2 , and ESX expression may represent a downstream mediator of ErbB 2 signaling and ErbB 2 induced gene expression . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Members of the erbB family receptor tyrosine kinases ( erbB 1 , erbB 2 , erbB 3 , and erbB 4 ) are overexpressed in a variety of human cancers and represent important targets for the structure based drug design . ^^^ In surface plasmon resonance ( BIAcore ) studies , the designed peptides have been shown to selectively bind to the erbB receptor ectodomains and isolated subdomain 4 of erbB 2 with submicromolar affinities and to inhibit heregulin induced interactions of erbB 3 with different erbB receptors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Given that a large proportion of human high grade gliomas over express the epidermal growth factor receptor ( EGFR ) and ErbB 2 , this study aimed to investigate whether an interaction exists between CD 44 and these receptor tyrosine kinases . ^^^ Here we present evidence that CD 44 co immunoprecipitates with EGFR and ErbB 2 in the glioma cell lines U87MG and SMA 560 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 2 and ErbB 3 do not quantitatively modulate ligand induced ErbB 4 tyrosine phosphorylation . ^^^ ErbB 2 is an `` orphan ' ' for which there is no naturally occurring , soluble ligand . ^^^ Thus , we hypothesized that ErbB 2 enhances ligand induced ErbB family receptor signalling through mass action . ^^^ One expresses ErbB 4 alone , the second expresses ErbB 2 and ErbB 4 , and the third expresses ErbB 3 and ErbB 4 . ^^^ ErbB 2 and ErbB 3 do not affect the amount of ligand induced ErbB 4 tyrosine phosphorylation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The ErbB 1 and ErbB 2 receptor tyrosine kinases ( RTKs ) play important roles in the development of numerous types of human cancer and , as such , have been pursued as anticancer targets . ^^^ The inhibitors used included monoclonal antibody ( mAb ) 4D5 , which targets ErbB 2 , and the small molecular weight kinase inhibitors CGP 59326 and PKI 166 , which block the activity of ErbB 1 or both ErbB 1 and ErbB 2 , respectively . ^^^ We had reported previously that although both BT 474 and MKN 7 cells overexpress ErbB 2 , only BT 474 cells show an antiproliferative response to mAb 4D5 treatment . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In A 549 and H 322 cells , which express a detectable amount of EGF R ( ErbB 1 ) , ErbB 2 , ErbB 3 , and ErbB 4 receptors , the LA 1 mAb induces up regulation of the E cadherin / catenin complex ( alpha , beta , and gamma catenins ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We also determined the concentrations of HA , erbB 2 oncoprotein , epidermal growth factor receptor ( EGFR ) , CD44s , CD44v5 and CD44v6 in cell surfaces . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Significantly , the mechanisms controlling ligand stimulated proliferation through ErbB 2 are strikingly similar to the mechanisms through which overexpressed , constitutively activated , ErbB 2 orchestrates uncontrolled proliferation in cancer cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Role of the N terminus of epidermal growth factor in ErbB 2 / ErbB 3 binding studied by phage display . ^^^ Epidermal growth factor ( EGF ) binds with high affinity to the EGF receptor , also known as ErbB 1 , but upon replacement of the N terminal linear region by neuregulin ( NRG ) 1 or transforming growth factor ( TGF ) alpha sequences it gains in addition high affinity for ErbB 2 / ErbB 3 heterodimers . ^^^ To further dissect the ligand binding selectivity of the ErbB network , we have applied the phage display technique to examine the role of the linear N terminal region in EGF for interaction with ErbB 2 / ErbB 3 heterodimers . ^^^ A library of EGF variants was constructed in which residues 2 , 3 , and 4 were randomly mutated , followed by selection for binding to intact MDA MB 453 cells that overexpress ErbB 2 and ErbB 3 but lack ErbB 1 . ^^^ Analysis of the selected phage EGF variants revealed clones with high binding affinity to ErbB 2 / ErbB 3 while maintaining high affinity to ErbB 1 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
For example , deregulated signaling by ErbB 1 and ErbB 2 is observed in many human malignancies . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Estrogen receptor ( ER ) , progesterone receptor , epidermal growth factor receptor , erbB 2 , and HSP 27 were measured by immunohistochemistry in paraffin fixed material obtained from the primary tumors at initial surgery . ^^^ Using CA 125 criteria , comparison of the CA 125 stable / responding disease with progressive disease indicated that tumors with higher ER ( P = 0 . 013 ) , lower erbB 2 ( P = 0 . 026 ) , and higher epidermal growth factor receptor ( P = 0 . 009 ) were associated with CA 125 stable / responsive disease . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Induction or suppression of expression of cytochrome C oxidase subunit 2 by heregulin beta 1 in human mammary epithelial cells is dependent on the levels of ErbB 2 expression . ^^^ Heregulin ( HRG ) activates the ErbB 2 via induction of heterodimerization with ErbB 3 and ErbB 4 receptors . ^^^ Two nontransformed human mammary epithelial cell lines , the HB 2 and the HB 2 ( ErbB 2 ) ( the HB 2 engineered to overexpress ErbB 2 ) , displayed an opposite response to HRG mediated regulation . ^^^ HRG upregulated mRNA expression of COXII in the HB 2 cells , but suppressed COXII expression in the HB 2 ( ErbB 2 ) cells . ^^^ A human breast cancer cell line ( T47D ) , which expresses ErbB 2 at a level similar to that of the HB 2 cells , also responded to HRG by increasing COXII mRNA levels . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunolabeling of heregulin , a growth factor that enhances cell proliferation in damaged utricles , and one of its binding receptors , ErbB 2 , has been briefly described in the P 3 rat cochlea and utricle [ Zheng et al . ( 1999 ) J . ^^^ Here we describe the immunolabeling patterns for heregulin , ErbB 2 , ErbB 3 and ErB 4 in the cochlea , spiral ganglion , utricle and saccule of the adult chinchilla using confocal microscopy . ^^^ In the cochlea , intense to moderate ErbB 2 immunolabeling was evident in the cytoplasm of pillar cells , outer hair cells ( OHCs ) , border cells , stria vascularis and spiral ligament ; moderate ErbB 2 immunolabeling was present in the cytoplasm of the hair cell and supporting cell layers of the utricle and saccule . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Heart valve mesenchyme formation is dependent on hyaluronan augmented activation of ErbB 2 ErbB3 receptors . ^^^ We show that hyaluronan deficient AVC explants from Has 2 ( / ) embryos , which normally lack mesenchyme formation , are rescued by heregulin treatment , which restores phosphorylation of ErbB 2 and ErbB 3 . ^^^ These events were blocked using a soluble ErbB 3 molecule , as well as with an inhibitor of ErbB 2 , herstatin . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Differential cytoskeletal association of ErbB 1 and ErbB 2 during keratinocyte differentiation . ^^^ ErbB 1 and ErbB 2 display differential subcellular localization in human skin and cultured keratinocytes . ^^^ To determine whether ErbB 1 and ErbB 2 also differ in cytoskeletal binding properties , normal human keratinocytes grown under conditions favoring a basal or differentiated phenotype were repeatedly extracted in a non ionic detergent buffer . ^^^ In basaloid keratinocytes , cytoskeletal association of ErbB 1 and ErbB 2 was limited . ^^^ ErbB 1 ( approximately 5 % ) was tightly associated with the cytoskeleton , compared to < 1 % of ErbB 2 ( p=0 . 004 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The erbB receptor family is part of the receptor tyrosine kinase superfamily and consists of four members , erbB 1 , erbB 2 , erbB 3 , and erbB 4 . ^^^ Clinically , blockade of the erbB 2 receptor has recently been shown to provide benefit in a subset of chemotherapy resistant breast cancer patients . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The 1p34 locus containing MYCL 1 , 2p24 ( MYCN ) , 7p12 ( EGFR ) , and 12q14 ( MDM 2 ) were amplified in one of the 32 cases ( 3 % ) , and the 17q12 locus ( ERBB 2 ) and 8p11 ( FGFR 1 ) in two of the 32 cases ( 6 % ) , while only the 11q13 locus ( Cyclin D 1 , FGF 4 , and EMS 1 ) was frequently amplified ( 28 % , 9 / 32 ) , demonstrating this locus to be a major target in ESCCs . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunoblotting analyses revealed that 23 of the 24 cell lines examined express the EGFR , and 24 of 24 express the related tyrosine kinase erbB 2 , whereas erbB 3 was detected in only 6 of 24 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 4 associates with the PSD 95 ( also known as SAP 90 ) family members including PSD 95 , SAP 97 , and SAP 102 whereas ErbB 2 interacts with Erbin and PICK 1 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The prognostic biomarkers chosen for comparison represented surrogate measures of tumor : ( 1 ) . proliferation , growth and genetic instability ( mitotic and apoptotic indices , Ki 67 / MIB 1 positivity , nuclear grade , p 53 positivity ) , ( 2 ) . endocrine dependence ( estrogen receptor ( ER ) , progesterone receptors ( PR ) , pS 2 , Bcl 2 ) , ( 3 ) . growth factor receptor dependence ( ErbB 2 , EGFR / ErbB1 ) , and ( 4 ) . angiogenic , invasive and proteolytic potential ( uPA , PAI 1 , Cathepsin D , VEGF ) . ^^^ In contrast , significant inverse correlations ( |r| > 0 . 1 ; P < or =0 . 05 ) were observed for all measures of tumor growth and genetic instability as well as growth factor receptor overexpression ( ErbB 2 or EGFR positivity ) . ^^^ In particular , breast tumors arising in older patients have slower growth rates , are more likely to be ER positive , and are less likely to be p 53 positive , EGFR positive or ErbB 2 positive . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
EGFR signaling may be increased by a number of mechanisms in addition to high expression levels of EGFR , including receptor mutations , heterodimerization with other members of this receptor family such as HER 2 ( erbB 2 ) , increased expression of ( autocrine / paracrine ) ligands , and alterations in molecules that control receptor signaling output . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 2 is a ligand less member of the ErbB receptor family that functions as a coreceptor with EGFR , ErbB 3 , and ErbB 4 . ^^^ Targeting ligand activated ErbB 2 signaling inhibits breast and prostate tumor growth . ^^^ Here , we describe an approach to target ErbB 2 ' s role as a coreceptor using a monoclonal antibody , 2C4 , which sterically hinders ErbB 2 ' s recruitment into ErbB ligand complexes . ^^^ Inhibition of ligand dependent ErbB 2 signaling by 2C4 occurs in both low and high ErbB 2 expressing systems . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
One of the critical intracellular signal transduction pathways involves the binding of the Grb 2 SH2 domain to the phosphotyrosine ( pTyr ) motifs on growth factor receptors , such as epidermal growth factor receptor ( EGFR ) and erbB 2 , leading to downstream activation of the oncogenic Ras signaling pathway . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The ErbB family of receptor tyrosine kinases comprise four members : EGFR , ErbB 2 , ErbB 3 and ErbB 4 . ^^^ ErbB receptors , particularly EGFR and ErbB 2 are commonly deregulated in certain prevalent forms of human cancer . ^^^ ErbB receptors , particularly EGFR and ErbB 2 are commonly deregulated in certain prevalent forms of human cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Here we show that a small molecule , GW 572016 , potently inhibits both EGFR and erbB 2 tyrosine kinases leading to growth arrest and / or apoptosis in EGFR and erbB 2 dependent tumor cell lines . ^^^ GW 572016 markedly reduced tyrosine phosphorylation of EGFR and erbB 2 , and inhibited activation of Erk1 / 2 and AKT , downstream effectors of proliferation and cell survival , respectively . ^^^ These observations were reproduced in vivo , where GW 572016 treatment inhibited activation of EGFR , erbB 2 , Erk1 / 2 and AKT in human tumor xenografts . ^^^ Inhibition of activated AKT in EGFR or erbB 2 dependent tumors by GW 572016 may lead to tumor regressions when used as a monotherapy , or may enhance the anti tumor activity of chemotherapeutics , since constitutive activation of AKT has been linked to chemo resistance . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Over expression studies have demonstrated that RALT ( receptor associated late transducer ) is a feedback inhibitor of ErbB 2 mitogenic and transforming signals . ^^^ Here , we show that physiological levels of RALT effectively suppress ErbB 2 mitogenic signals . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The level of extracellular signal regulated kinase activation correlated with the response to PKI 166 treatment , whereas the expression levels of ErbB 1 and ErbB 2 did not . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 2 is resistant to degradation mediated by c Cbl , the E 3 ubiquitin ligase responsible for ligand induced ubiquitination of ErbB 1 ( epidermal growth factor receptor ) . ^^^ Overexpression of the transmembrane receptor tyrosine kinase ErbB 2 is common in multiple malignancies , including breast and ovarian cancer . ^^^ Because of its resistance to degradation , ErbB 2 is the preferred dimerization partner for other members of the ErbB family , and its overexpression in vivo is associated with poor prognosis . ^^^ We now show that the chaperone binding ubiquitin ligase CHIP efficiently ubiquitinates and down regulates ErbB 2 . ^^^ CHIP expression shortens the half life of both nascent and mature ErbB 2 protein . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
There was no correlation of erbB 2 expression with integrin expressions . ^^^ Then we transfected erbB 2 gene into MDA MB 435 and found the induction of erbB 3 expression but not erbB 1 and erbB 4 . ^^^ However , erbB 2 transfection had no effect on the expression of alpha 6 and beta 4 integrin subunits . ^^^ These data suggest that the expression of alpha 5 and alpha 6 integrins may contribute to metastasis , and that the regulation of erbB 2 and alpha 6 integrin expressions is independent in breast cancer cells . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : This study was designed to investigate the biological and therapeutic significance of ERBB 1 , ERBB 2 , ERBB 3 , and ERBB 4 in childhood ependymoma . ^^^ RESULTS : Coexpression of ERBB 2 and ERBB 4 was identified in over 75 % of tumors . ^^^ Ligand dependent activation of ERBB receptor signaling in cultured ependymoma cells resulted in AKT phosphorylation and cellular proliferation that was significantly blocked in a dose dependent manner using WAY 177820 , a novel inhibitor of ERBB 2 tyrosine kinase activity . ^^^ An analysis of ERBB 2 and ERBB 4 expression , in association with Ki 67 LI and the degree of surgical resection , may provide an accurate tool for assessing disease risk in children with this disease . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We found the mean AGCNs of the oncogenes equal 1 . 18 for erbB 1 [ amplification was found in 11 / 35 cases ( 31 % ) and deletion in 6 / 35 cases ( 17 % ) ] , 2 . 00 for erbB 2 [ amplification was found in 8 / 34 cases ( 24 % ) , no deletion was found ] , 1 . 36 for erbB 3 [ amplification was found in 4 / 36 cases ( 11 % ) and deletion in 1 / 36 cases ( 3 % ) ] , and 1 . 22 for erbB 4 [ amplification was found in 5 / 30 cases ( 17 % ) and deletion in 1 / 30 cases ( 3 % ) ] . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Lipid rafts and the local density of ErbB proteins influence the biological role of homo and heteroassociations of ErbB 2 . ^^^ In this report , we describe the states of association of ErbB 2 and their relationship to local ErbB 3 density and lipid rafts based on quantitative fluorescence microscopy of SKBR 3 breast cancer cells . ^^^ Clusters of ErbB 2 colocalized with lipid rafts identified by the GM 1 binding B subunit of cholera toxin . ^^^ Pixel by pixel analysis of fluorescence resonance energy transfer between labeled antibodies indicated that the homoassociation ( homodimerization ) of ErbB 2 was proportional to the local density of ErbB 2 and inversely proportional to that of ErbB 3 and of the raft specific lipid GM 1 . ^^^ Crosslinking lipid rafts with the B subunit of cholera toxin caused dissociation of the rafts and ErbB 2 clusters , an effect that was independent of the cytoskeletal anchoring of ErbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The neuregulin ( NRG ) / epidermal growth factor ( EGF ) family of growth factors consists of several ligands that specifically activate four erbB receptor tyrosine kinases , namely erbB 1 ( EGF R ) , erbB 2 ( neu ) , erbB 3 , and erbB 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
This study is the first to examine the role of all members of the ErbB tyrosine kinase receptors ( epidermal growth factor receptor [ EGFR ] , ErbB 2 , ErbB 3 , or ErbB 4 ) , expressed singly or as paired receptor combinations , in the regulation of angiogenesis both in vitro and in vivo . ^^^ Comparison of all receptor combinations reveals that EGFR / ErbB 2 and ErbB 2 / ErbB 3 heterodimers are the most potent inducers of vascular endothelial growth factor ( VEGF ) mRNA expression compared with EGFR / ErbB 3 , EGFR / ErbB 4 , ErbB 2 / ErbB 4 , and ErbB 3 / ErbB 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
An ErbB 2 Muc4 complex in rat ocular surface epithelia . ^^^ PURPOSE : To show the presence and localization of type 1 growth factor receptors ( ErbB 2 , ErbB 3 and ErbB 4 ) in rat corneal and conjunctival epithelia and investigate the association of ErbB 2 with its intramembrane ligand Muc 4 . ^^^ Sequential immunoprecipitation and immunoblot analyses were performed on epithelial lysates to investigate the presence of a complex of Muc 4 and ErbB 2 in corneal and conjunctival epithelia . ^^^ RESULTS : Immunocytochemical staining demonstrated the presence of ErbB 2 , ErbB 3 and ErbB 4 growth factor receptors throughout the rat corneal and conjunctival epithelia . ^^^ Co immunoprecipitation of the epithelial lysates demonstrated that Muc 4 and ErbB 2 are present as a complex . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Using real time quantitative PCR assays , mRNA levels of ERalpha , ERbeta , epidermal growth factor receptor , ErbB 2 , ErbB 3 , ErbB 4 , ERRalpha , ERRbeta , and ERRgamma were determined in unselected primary breast tumors ( n = 38 ) and normal mammary epithelial cells enriched from reduction mammoplasties ( n = 9 ) . ^^^ ERRalpha levels also correlated with expression of ErbB 2 ( Spearman ' s rho , P = 0 . 005 ) , an indicator of aggressive tumor behavior . ^^^ Thus , ERRalpha was the most abundant nuclear receptor in a subset of tumors that tended to lack functional ERalpha and expressed ErbB 2 at high levels . ^^^ Consequently , ERRalpha may potentiate constitutive transcription of estrogen response element containing genes independently of ERalpha and antiestrogens in ErbB 2 positive tumors . ^^^ Hence , ERRalpha and ERRgamma status may be predictive of sensitivity to hormonal blockade therapy , and ERRalpha status may also be predictive of ErbB 2 based therapy such as Herceptin . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
EGFR is a member of the ErbB family of receptors which also includes ErbB 2 , ErbB 3 , and ErbB 4 . ^^^ EGFR is a member of the ErbB family of receptors which also includes ErbB 2 , ErbB 3 , and ErbB 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
RESULTS : The epidermal growth factor receptor , ErbB 2 , and ErbB 3 were the only ErbB proteins detected in the liver parenchyma on embryonic day 19 . ^^^ ErbB 2 disappeared by the third week after birth and could not be appreciably induced in the adult animal by partial hepatectomy . ^^^ ErbB 2 was also detected in multipotent stem ( RLE ) and hepatoma ( H4IIe ) cell lines as well as in fetal , but not adult , hepatocyte cultures . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The epidermal growth factor receptor ( EGFR ) and ErbB 2 transmembrane tyrosine kinases are currently being targeted by various mechanisms in the treatment of cancer . ^^^ GW 2016 is a potent inhibitor of the ErbB 2 and EGFR tyrosine kinase domains with IC 50 values against purified EGFR and ErbB 2 of 10 . 2 and 9 . 8 nM , respectively . ^^^ This report describes the efficacy in cell growth assays of GW 2016 on human tumor cell lines overexpressing either EGFR or ErbB 2 : HN 5 ( head and neck ) , A 431 ( vulva ) , BT 474 ( breast ) , CaLu 3 ( lung ) , and N 87 ( gastric ) . ^^^ After 3 days of compound exposure , average IC 50 values for growth inhibition in the EGFR and ErbB 2 overexpressing tumor cell lines were < 0 . 16 microM . ^^^ Inhibition of EGFR and ErbB 2 receptor autophosphorylation and phosphorylation of the downstream modulator , AKT , was verified by Western blot analysis in the BT 474 and HN 5 cell lines . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The magnitude of NRG growth response was significantly associated with erbB 2 expression levels . ^^^ NRG 1alpha and 1beta ( 1 nM ) growth stimulated cell lines PE 01 and PE 06 demonstrated increased tyrosine phosphorylation of erbB 2 and elevated tyrosine phosphorylation of ERK 1 and ERK 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Transactivation of ErbB 1 and ErbB 2 receptors by angiotensin 2 in normal human prostate stromal cells . ^^^ ErbB 1 and ErbB 2 receptors were activated by HB EGF . ^^^ Furthermore , Ang 2 was able to transactivate both ErbB 1 and ErbB 2 , and this transactivation activity could be abolished by pretreatment with [ Glu 52 ] diphtheria toxin / CRM197 , a specific inhibitor of HB EGF bioactivity . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Flow cytometry indicated that in both cell types , gastrin increased MAP kinase via activation of EGF R but not FGF R 1 or erbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In this context , we investigated whether neutrophil elastase may regulate expression of MUC 4 , a membrane tethered mucin that has recently been identified as a ligand for ErbB 2 , the major heterodimerization partner of the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We have established a series of stable , monoclonal 32D derived cell lines that express the epidermal growth factor ( EGF ) receptor , ErbB 2 , or a combination of both at different ratios . ^^^ Increasing the relative expression of ErbB 2 leads to an increase in the fraction of high affinity class receptors observed , without altering the total number of EGF binding sites . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
MUC 4 is a novel intramembrane ligand for the receptor tyrosine kinase ErbB2 / HER2 / Neu , triggering a specific phosphorylation of the ErbB 2 in the absence of other ErbB ligands and potentiating phosphorylation and signaling through the ErbB2 / ErbB3 heterodimeric receptor complex formed in the presence of neuregulin . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ERBB 2 up regulates S100A4 and several other prometastatic genes in medulloblastoma . ^^^ Previously , we reported that overexpression of ERBB 2 in medulloblastoma is associated with poor prognosis and metastasis . ^^^ Here , we demonstrate that ERBB 2 overexpression increases the migration of medulloblastoma cells across basement membranes in vitro . ^^^ Furthermore , using microarray expression profiling , we show that ERBB 2 up regulates the expression of prometastatic genes in medulloblastoma cells . ^^^ We demonstrate that S100A4 is a direct target of ERBB 2 signaling in medulloblastoma cells via a pathway involving phosphatidylinositol 3 kinase , AKT 1 , and extracellular signal regulated kinase 1 / 2 and that levels of ERBB 2 and S100A4 are tightly correlated in samples of primary medulloblastoma . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Western blot and immunofluorescence confirmed the expression of multiple NRG isoforms and the ErbB 2 , ErbB 3 , and ErbB 4 receptors in adult skeletal muscle . ^^^ Thus two distinct modes of exercise activated processing of NRG with concomitant stimulation of ErbB 2 , ErbB 3 , and ErbB 4 signaling in vivo . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Thrombin phosphorylates EGFRs and ErbB 2 via a PP 1 sensitive pathway in PAR 1 ( / ) cells that stably overexpress PAR 4 ; the Src mediated pathway for EGFR / ErbB2 transactivation underlies the protracted phases of thrombin dependent extracellular signal regulated kinase activation in PAR 1 ( / ) cells that overexpress PAR 4 and in cardiomyocytes . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Given these NRG 1 actions , we hypothesized that the synaptic loss , gliosis , inflammation , and neuronal death occurring in Alzheimer disease ( AD ) is associated with altered expression of NRG 1 and its receptors ( the erbB 2 , erbB 3 , and erbB 4 membrane tyrosine kinases ) . ^^^ All 4 molecules are associated with neuronal cell bodies , but only NRG 1 , erbB 2 , and erbB 4 are present in synapse rich regions . ^^^ NRG 1 and erbB 4 , as well as erbB 2 , are similarly associated with neuritic plaques in the doubly transgenic mice . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
To analyze whether there is a link between these two regulatory molecules , we studied the effects of ErbB 2 activation by heregulin ( HRG ) on BRCA 1 function . ^^^ Accordingly , T47D cells grown on LAM had the greatest increase in ErbB 2 activation , PI3K activity , and phosphorylation of Akt . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
DN erbB 4 expression is most abundant in hypothalamic astrocytes , where it blocks the ligand dependent activation of glial erbB 4 and erbB 2 receptors , without affecting erbB 1 ( EGF ) receptor signaling . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
This is also a region in which the epidermal growth factor receptor and ErbB 2 kinase domains differ significantly in sequence . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
It has been reported that overexpression of the epidermal growth factor receptor ( erbB 1 ) or its homologous receptor , HER 2 ( erbB 2 ) , can confer antiestrogen resistance to estrogen receptor ( ER ) positive human breast cancer cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Selective formation of ErbB 2 / ErbB 3 heterodimers depends on the ErbB 3 affinity of epidermal growth factor like ligands . ^^^ EGF like growth factors activate their ErbB receptors by promoting receptor mediated homodimerization or , alternatively , by the formation of heterodimers with the orphan ErbB 2 through an as yet unknown mechanism . ^^^ To investigate the selectivity in dimer formation by ligands , we have applied the phage display approach to obtain ligands with modified C terminal residues that discriminate between ErbB 2 and ErbB 3 as dimerization partners . ^^^ We used the epidermal growth factor / transforming growth factor alpha chimera T1E as the template molecule because it binds to ErbB 3 homodimers with low affinity and to ErbB 2 / ErbB 3 heterodimers with high affinity . ^^^ These variants were also potent ligands for ErbB 2 / ErbB 3 heterodimers despite negative selection for such heterodimers . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The growth factor heregulin ( HRG ) , expressed in about 30 % of breast cancer tumors , activates the erbB 2 receptor via induction of heterodimeric complexes of erbB 2 with erbB 3 or erbB 4 . ^^^ Our investigation into whether HRG is a factor likely to promote tumor formation independently of erbB 2 overexpression concludes that blockage of HRG expression suppresses the aggressive phenotype of MDA MB 231 breast cancer cells by inhibiting cell proliferation , preventing anchorage independent growth , and suppressing the invasive potential of the cells in vitro . ^^^ Our study is the first report and serves as a proof of the concept that HRG is a key promoter of breast cancer tumorigenicity and metastasis independently of erbB 2 overexpression and should be deemed a potential target in developing therapies for breast cancer . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
These ectodomains mediate ErbB 2 dimerisation with itself or with other members of the epidermal growth factor receptor ( EGFR ) family , events essential to both ErbB 2 signaling and the development of certain malignancies . ^^^ A molecular model of ErbB 2 ectodomains was then constructed based on the recently published coordinates of the EGFR ( EGFR ) model . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Alpha6beta1 integrin induces proteasome mediated cleavage of erbB 2 in breast cancer cells . ^^^ ErbB 2 and alpha 6 integrin have been implicated in malignancy of breast cancer cells . ^^^ Here we have determined the influence of alpha6beta1 integrin on erbB 2 signaling in anchorage independent growth , using MDA MB 435 breast cancer cells . ^^^ Firstly , we transfected the cells with erbB 2 cDNA , and isolated cells with high or low levels of alpha6beta1 integrin by cell sorting ( alpha6H ErbB and alpha6L ErbB ) . ^^^ Again , heregulin beta 1 enhanced the growth of erbB 2 cDNA transfected beta 4 deltacyt cells , but not mock cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 2 pathways in heart and neural diseases . ^^^ The proto oncogene ErbB 2 ( also known as c neu or HER 2 in humans ) encodes a receptor tyrosine kinase that is frequently overexpressed in human tumors . ^^^ Biochemical and genetic experiments have shown that ErbB 2 acts as a coreceptor for other members of the ErbB family of receptor tyrosine kinases . ^^^ Of particular medical relevance are recent findings that relied on tissue specific mutation of ErbB 2 in cardiomyocytes , which revealed an essential function of ErbB 2 in normal heart physiology and demonstrated that loss of cardiac ErbB 2 can cause dilated cardiomyopathy in adult mice . ^^^ Thus , ErbB 2 is important not only in development , but also for the correct functioning of the differentiated myocardium . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In addition , erbB 2 , an integral member of the heterodimeric neuregulin 1 receptor , has been shown to be overexpressed in human glioma biopsies . ^^^ Using antibodies specific for erbB 2 and erbB 3 , we show that these receptors localize preferentially in regions of the plasma membrane which are involved in facilitating cellular movement . ^^^ Here , erbB 2 colocalizes and coimmunoprecipitates with members of the focal complex including beta 1 integrin and focal adhesion kinase . ^^^ These effects of neuregulin 1 appear to involve the activation of focal adhesion kinase , which occurs downstream from erbB 2 receptor stimulation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Keratinocytes express the erbB 1 ( also called EGF R , HER 1 ) , the erbB 2 ( also known as neu or HER 2 ) , and the erbB 3 ( HER 3 ) subtypes . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 2 degradation mediated by the co chaperone protein CHIP . ^^^ ErbB 2 overexpression contributes to the evolution of a substantial group of human cancers and signifies a poor clinical prognosis . ^^^ Thus , down regulation of ErbB 2 signaling has emerged as a new anti cancer strategy . ^^^ Ubiquitinylation , mediated by the Cbl family of ubiquitin ligases , has emerged as a physiological mechanism of ErbB receptor down regulation , and this mechanism appears to contribute to ErbB 2 down regulation induced by therapeutic anti ErbB 2 antibodies . ^^^ Hsp 90 inhibitory ansamycin antibiotics such as geldanamycin ( GA ) induce rapid ubiquitinylation and down regulation of ErbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
GH causes phosphorylation of epidermal growth factor receptor ( EGFR ; ErbB 1 ) and its family member , ErbB 2 . ^^^ We now further explore GH induced EGFR phosphorylation in 3T3 F442A , a preadipocytic fibroblast cell line that expresses endogenous GH receptor , EGFR , and ErbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 2 ( also called HER2 / neu ) and ErbB 3 are closely related to the epidermal growth factor receptor ( EGFR / ErbB 1 ) , but unlike EGFR , ErbB 2 is a ligandless receptor , whereas ErbB 3 lacks tyrosine kinase activity . ^^^ The deaf and the dumb : the biology of ErbB 2 and ErbB 3 . ^^^ Hence , both ErbB 2 and ErbB 3 are active only in the context of ErbB heterodimers , and ErbB 2 . ^^^ This review highlights recent structural insights into the mechanism of ligand induced heterodimer formation , and concentrates on signaling pathways employed by ErbB 2 and ErbB 3 in normal and in malignant cells . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
EGFR , erbB 2 protein , CD44s , CD44v5 and CD44v6 levels at cell surfaces were determined . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
HER 2 ( also known as Neu , ErbB 2 ) is a member of the epidermal growth factor receptor ( EGFR ; also known as ErbB ) family of receptor tyrosine kinases , which in humans includes HER 1 ( EGFR , ERBB 1 ) , HER 2 , HER 3 ( ERBB 3 ) and HER 4 ( ERBB 4 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 2 and its ligand Muc 4 ( sialomucin complex ) in rat lacrimal gland . ^^^ Analyses of ErbB 2 and the Muc4 / SMC ErbB 2 complex in the lacrimal gland suggest a second function for Muc4 / SMC , a role in cell regulation through ErbB signaling . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The cardiac valve and the ventricular chamber phenotypes resembled those displayed by mice lacking EGFR , a receptor for HB EGF , and by mice conditionally lacking ErbB 2 , respectively . ^^^ HB EGF induced tyrosine phosphorylation of ErbB 2 and ErbB 4 , and to a lesser degree , of EGFR in cardiac myocytes . ^^^ In addition , constitutive tyrosine phosphorylation of both ErbB 2 and ErbB 4 was significantly reduced in HB ( del / del ) hearts . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Previously , we have shown that intrabodies targeted to the lumen of the endoplasmic reticulum prevent the transit of EGFR or the related ErbB 2 molecule to the cell surface , thereby inactivating their transforming potential . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Discovery and biological evaluation of potent dual ErbB 2 / EGFR tyrosine kinase inhibitors : 6 thiazolylquinazolines . ^^^ We have identified a novel class of 6 thiazolylquinazolines as potent and selective inhibitors of both ErbB 2 and EGFR tyrosine kinase activity , with IC ( 50 ) values in the nanomolar range . ^^^ These compounds inhibited the growth of both EGFR ( HN 5 ) and ErbB 2 ( BT 474 ) over expressing human tumor cell lines in vitro . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Our particular emphasis in this review will be on how ErbB receptors , in particular ErbB 1 and ErbB 2 , contribute to processes linked to cancer progression . ^^^ Importantly , in keeping with the emerging theme that ErbB receptors do not function in isolation , we will focus on receptor cooperativity , i . e . , ErbB 1 cooperates with other classes of receptors , and the ligand less ErbB 2 functions as a heterodimer with other ErbBs . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The overall prevalence of amplifications of five oncogenes analyzed was 34 . 5 % for CCND 1 , 12 . 7 % for EGFR , 8 . 8 % for MYC , 6 . 2 % for ZNF 217 , and 3 . 6 % for ERBB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Furthermore , the inhibition of UVB induced apoptosis could also be observed using neutralizing antibodies to either erbB 1 or erbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The androgen dependent prostate cancer cell line , LNCaP , expresses the EGFR as well as two additional members of the family ; ErbB 2 and ErbB 3 , which can be activated by neuregulin ( NRG ) isoforms . ^^^ RESULTS : Our results demonstrate that NRG activates ErbB 2 / ErbB 3 heterodimers and induces cell death of LNCaP cells . ^^^ By contrast , EGF activates ErbB 1 / ErbB 1 or ErbB 1 / ErbB 2 dimers and induces cell growth and survival . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Erbb 2 regulates neuromuscular synapse formation and is essential for muscle spindle development . ^^^ To analyze the function of Erbb 2 in this process , we have inactivated the Erbb 2 gene in developing muscle fibers by Cre / Lox mediated gene ablation . ^^^ Sensory Ia afferent neurons establish initial contact with Erbb 2 deficient myotubes . ^^^ Taken together , our data suggest that Erbb 2 signaling regulates the formation of both neuromuscular synapses and muscle spindles . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
RT PCR analysis revealed that the EGF receptors erbB 1 , erbB 2 , erbB 3 and erbB 4 were expressed at all stages of the spermatogenic wave , whereas differential expression was found in isolated Leydig , Sertoli and peritubular cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Furthermore , topical application of tyrphostin AG 1478 or AG 825 , specific inhibitors of EGFR and ErbB 2 , respectively , completely inhibited new hair growth in wild type mice but not in transgenic mice . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
RESULTS : In the absence of androgens , the cells have low levels of ErbB 1 and relatively high levels of ErbB 2 . ^^^ Addition of androgens to the medium reversed the ratio ; ErbB 1 levels rose and ErbB 2 levels dropped in response to treatment with the synthetic hormone , R 1881 . ^^^ The androgen induced proliferation of LNCaP cells was completely inhibited by the addition of the small molecule ErbB 1 tyrosine kinase inhibitors CGP 59326 and the bispecific inhibitor ( PKI 166 ) for ErbB 1 and ErbB 2 to the culture medium . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Heregulin ( HRG ) is an activator of the erbB 2 , erbB 3 and erbB 4 ( erbB 2 / 3 / 4 ) signaling pathway . ^^^ Transfection of full length HRG cDNA into the estrogen ( E 2 ) dependent cell line MCF 7 promoted an invasive E 2 independent phenotype , as well as persistent activation of the erbB 2 / 3 / 4 receptors . ^^^ Our data show that the HRG / M sequences are sufficient to sensitize MCF 7 cells to Doxo , and provide evidence that this sensitization is independent of erbB 2 activation . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The epidermal growth factor receptor ( EGFR ) and related family members ( ERBB 2 , ERBB 3 , and ERBB 4 ) previously have been shown to play pivotal roles in the development of female reproductive tissues , in blastocyst implantation , and in placental differentiation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
To investigate the significance of these mechanisms on an early stage of human breast tumour growth , we studied the expression of EGFR ( ErbB 1 ) , HER 2 / neu ( ErbB 2 ) , cyclin D 1 , p 21 and p 53 as well as oestrogen ( ER ) and progesterone receptor ( PgR ) in paraffin sections of 45 ductal carcinoma in situ ( DCIS ) by immunohistochemistry . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We now report that RALT binds to ligand activated epidermal growth factor receptor ( EGFR ) , ErbB 4 and ErbB 2 . ^^^ The ErbB 2 interacting protein receptor associated late transducer ( RALT ) was previously identified as a feedback inhibitor of ErbB 2 mitogenic signals . ^^^ Remarkably , RALT deltaEBR retained the ability to suppress largely the proliferative activity of ErbB 2 . ^^^ ErbB 3 dimers over a wide range of ligand concentrations , indicating that RALT can intercept ErbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Relative to nontransformed Schwann cells , JS 1 cells overexpress the NRG 1 receptor erbB 3 and its erbB 2 coreceptor ; JS 1 erbB2 transcripts show no evidence of the activating mutation commonly found in N ethyl N nitrosourea induced neoplasms . ^^^ Even in unstimulated JS 1 cells , however , erbB 2 and erbB 3 are constitutively tyrosine phosphorylated . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Three lines of evidence confirmed the EGFR is a potential target of flavopiridol trastuzumab synergy : ( a ) EGFR protein expression was rapidly and completely lost after combination treatment ; ( b ) a cell line that expresses amplified levels of both erbB 2 and the EGFR was resistant to the combined drugs ; and ( c ) treatment with epidermal growth factor prevented any therapeutic effects of flavopiridol and trastuzumab , singly or in combination . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The presence of the EGF receptors EGFR , ErbB 2 , and ErbB 3 was confirmed through Western blot analysis of cell lysates . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Expression of epidermal growth factor receptor ( EGFr ) , erbB 2 , and erbB 3 , but not erbB 4 , was detected throughout the epidermis , although labeling for erbB 2 and erbB 3 was accentuated in the upper spinous layers , and EGFr was more strongly labeled in basal cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Coimmunoprecipitation experiments also indicated that Grb 7 and NIK could be simultaneously recruited into signaling complexes of all known EGF / heregulin receptors , including EGFR , ErbB 2 , ErbB 3 , and ErbB 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Systematic modification of the 4 anilino functionality of a selective quinazoline inhibitor of the epidermal growth factor receptor ( EGFR ) tyrosine kinase can invert selectivity to favor inhibition of the highly homologous erbB 2 tyrosine kinase . ^^^ The most potent and selective erbB 2 inhibitor of the analog series has anti proliferative activity against an erbB 2 overexpressing cell line that was lacking in the original EGFR selective compound . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB receptors ( ErbB 1 / epidermal growth factor receptor , ErbB 2 , ErbB 3 , and ErbB 4 ) were stably overexpressed in a polyclonal cell population as single or paired combinations using murine and human breast cell models . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Investigation of ErbB 1 and ErbB 2 expression for therapeutic targeting in primary liver tumours . ^^^ AIMS : ErbB 1 and ErbB 2 expression was analysed in neoplastic and surrounding tissue in surgical specimens from 52 hepatocellular carcinomas and 48 intrahepatic cholangiocarcinomas , randomly chosen from cases surgically treated in this institution . ^^^ METHODS : ErbB 1 and ErbB 2 expression were evaluated immunohistochemically , the latter by Herceptest . ^^^ RESULTS : In normal / cirrhotic non neoplastic tissue , the ErbB 1 ( but not ErbB 2 ) antibody commonly stained normal hepatocytes and mature intrahepatic ducts . ^^^ Neither ErbB 1 nor ErbB 2 expression correlated with any of the main clinical pathologic features or survival . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Among the best studied growth factor receptors are the two members of EGF receptor familiy EGFr ( ErbB 1 ) , and Her2 / neu ( ErbB 2 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
First , Notch 1 activation by neuronal contact induces the glial expression of the brain lipid binding protein ( BLBP ) and erbB 2 genes . ^^^ Interestingly , two different signaling pathways mediate these effects of Notch 1 on transcription , BLBP expression being dependent on Su ( H ) , whereas erbB 2 is regulated by a yet unidentified Notch 1 pathway . ^^^ The subsequent increase in erbB 2 receptor expression makes the glia more responsive to neuronal NRG , which then induces the morphological transformation into radial glia . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ERBB gene expression varied widely , by more than 2 orders of magnitude for ERBB 1 and ERBB 3 , more than 3 orders for ERBB 2 and more than 4 orders for ERBB 4 . ^^^ Compared to normal breast tissue , ERBB 1 was underexpressed ( 82 . 3 % of tumors ) , ERBB 2 ( 16 . 9 % ) and ERBB 3 ( 46 . 2 % ) were overexpressed and ERBB 4 was both underexpressed ( 24 . 6 % ) and overexpressed ( 29 . 2 % ) . ^^^ Relapse free survival ( RFS ) was shorter among patients with ERBB 3 overexpressing tumors ( p=0 . 0092 ) and longer among those with ERBB 4 underexpressing tumors ( p=0 . 0085 ) relative to patients with normal expression of the respective genes ; in contrast , RFS was not significantly influenced by ERBB 1 or ERBB 2 mRNA status . ^^^ ERBB gene expression varied widely , by more than 2 orders of magnitude for ERBB 1 and ERBB 3 , more than 3 orders for ERBB 2 and more than 4 orders for ERBB 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
BTC induced phosphorylation of all four EGF receptors present on HTASMCs : ErbB 1 , ErbB 2 , ErbB 3 , and ErbB 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Inhibition of ErbB 2 and ErbB 3 expression by quercetin prevents transforming growth factor alpha ( TGF alpha ) and epidermal growth factor ( EGF ) induced human PC 3 prostate cancer cell proliferation . ^^^ Because ErbB 2 receptor is involved in hormone independency for growth and metastasis of prostate cancer cells , the aim was to investigate the effects of quercetin on ErbB 2 and ErbB 3 expression and its critical components such as MAP kinase and PI 3 kinase . ^^^ Changes in ErbB 2 , ErbB 3 and components of MAPK and PI 3K pathways were analyzed by Western blot analysis . ^^^ Concomitantly , these treatments led to a dose dependent decrease in ErbB 2 , ErbB 3 and their basal autophosphorylation levels as compared to controls . ^^^ Co treating PC 3 cells with quercetin significantly attenuated EGF and TGF alpha induced growth and phosphorylation of ErbB 2 , ErbB 3 , c Raf , MAPK kinase 1 / 2 ( MEK1 / 2 ) , MAPK , Elk 1 and Akt 1 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Furthermore , expression of ErbB 1 alone or in combination with ErbB 2 in NIH3T3 cells up regulates Mcl 1 following EGF treatment . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Some data suggest that letrozole may be a more effective treatment than tamoxifen for patients with ER+ and / or PgR+ early breast cancers expressing ErbB 1 and / or ErbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Aberrant expression or activity of epidermal growth factor receptor ( EGFr ) or the closely related p 185 ( erbB 2 ) can promote cell proliferation and survival and thereby contribute to tumorigenesis . ^^^ CP 654577 is a potent inhibitor selective for p 185 ( erbB 2 ) , relative to EGFr tyrosine kinase , and selectively reduces erbB 2 autophosphorylation in intact cells . ^^^ CP 654577 warrants further evaluation in tumors with high expression of p 185 ( erbB 2 ) and may differ from selective EGFr inhibitors or nonselective dual EGFr / erbB2 inhibitors in efficacy and therapeutic index . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Overexpression of ErbB 2 enhances ethanol stimulated intracellular signaling and invasion of human mammary epithelial and breast cancer cells in vitro . ^^^ Particularly , ErbB 2 plays a pivotal role in ErbB mediated activities . ^^^ Here we demonstrated that amplification of ErbB 2 expression sensitized a specific cellular response to ethanol . ^^^ Human breast cancer cells or mammary epithelial cells with a high expression of ErbB 2 exhibited an enhanced response to ethanol stimulated cell invasion in vitro . ^^^ Ethanol also stimulated cell proliferation ; however , this stimulation was independent of ErbB 2 levels . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Endothelial derived heparin binding EGF like growth factor ( HB EGF ) was shown to mediate this process by signaling via ErbB 1 and ErbB 2 receptors in SMCs . 1 ) Analysis of ErbB ligands demonstrated that primary ECs expressed only HB EGF and neuregulin 1 . 2 ) Primary SMCs expressed ErbB 1 and ErbB 2 , but not ErbB 3 or ErbB 4 . 3 ) Consistent with their known receptor specificities , recombinant HB EGF , but not neuregulin 1 , stimulated tyrosine phosphorylation of ErbB 1 and ErbB 2 and migration in SMCs . 4 ) Neutralization of HB EGF or inhibition of ErbB 1 or ErbB 2 blocked 70 90 % of the potential of ECs to stimulate SMC migration . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Lapatinib ditosylate , an ErbB 2 and EGFR dual tyrosine kinase inhibitor , is being developed by GlaxoSmithKline plc for the potential treatment of solid tumors . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Experiments employing selective ErbB inhibitors demonstrate that the effect of estradiol on ER alpha expression and activity is mediated by ErbB 2 and not by EGFR . ^^^ Moreover , anchorage dependent and independent growth assays , cell cycle and membrane ruffling analyses showed that Akt exerts estrogen like activity on cell growth and membrane ruffling and that a selective ErbB 2 inhibitor , but not anti ErbB 2 antibodies directed to the extracellular domain , can block these effects . ^^^ In contrast , in cells stably transfected with either a dominant negative Akt or with R25C Akt , as well as in parental cells in the presence of a selective ErbB 2 inhibitor , the effect of estradiol on anchorage dependent and independent cell growth was inhibited by 50 75 and 100 % , respectively . ^^^ Taken together , our results suggest that estradiol treatment results in binding to membrane ER alpha and interaction with a heterodimer containing ErbB 2 , leading to tyrosine phosphorylation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The gene expression levels in the two model systems were found to be quite similar in relation to ERalpha , AIB 1 ( amplified in breast cancer 1 ) , breast cancer antiestrogen resistance gene 1 ( BCAR 1 ) and ErbB 2 mRNA expression , whereas significant differences were observed on the expression of ERbeta , multidrug resistance gene 1 ( MDR 1 ) , PR and EGFR . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 2 and EGFR are downmodulated during the differentiation of 3T3 L 1 preadipocytes . ^^^ We found that the Swiss 3T3 L 1 fibroblasts express erbB 2 , in addition to EGFR , and in a quantity comparable to or even greater than the breast cancer cell line T47D . ^^^ Proliferating cells increased erbB 2 and EGFR levels when reaching confluence up to 4 and 10 fold , respectively . ^^^ Differentiated cells presented a decreased expression of both erbB 2 and EGFR regardless of whether the cells were hormonally or spontaneously differentiated . ^^^ Heregulin alpha 1 and beta 1 , two EGF related factors , had no effect on erbB 2 or EGFR phosphorylation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 2 , a family member that has no ligand , has its dimerization arm constitutively exposed , and this explains several of its unique properties . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
On the cell surface we analyzed the concentrations of epidermal growth factor receptor ( EGFR ) , HA , erbB 2 oncoprotein , CD44s , CD44v5 and CD44v6 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
These paired specimens were simultaneously analyzed for Ki 67 , ER , progesterone receptor ( PgR ) , trefoil factor 1 ( PS 2 ) , HER 1 ( epidermal growth factor receptor ) , and HER 2 ( ErbB 2 or neu ) by semiquantitative immunohistochemistry . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In two further breast cancer lines ( T47D and HS578T ) PKB / Akt phosphorylation was dependent upon autocrine factors acting primary through the epidermal growth factor receptor ( EGFR ) and erbB 2 . ^^^ Further analysis revealed that constitutive PKB / Akt phosphorylation was associated with loss of PTEN phosphatase expression ( CAL 51 , MDA MB 468 , BT 549 cells ) and constitutive activation of erbB 2 ( SKBR 3 , BT 474 cells ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
On the other hand , trials with EGF receptor inhibitors in unselected populations have shown anywhere from modest to no clinical activity . 1 will contrast below aspects in the development of inhibitors of Abl , c Kit , HER2 / neu ( erbB 2 ) , and EGFR , highlight successes and pitfalls in this field , and propose some approaches for the future development of tyrosine kinase inhibitors in human cancer . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Expression of CD 82 causes a significant increase in the amount of EGFR and ErbB 2 in the light fractions of the sucrose gradient . ^^^ Although CD 82 is also associated with ErbB 2 and ErbB 3 , ligand induced assembly of the ErbB 2 ErbB3 complexes is not affected in CD 82 expressing cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Inhibitors of ErbB 2 kinase blocked STAT 3 activation , whereas inhibition of EGFR kinase led to a slight reduction of STAT 3 activation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Overexpression of human EGF receptor HER 2 ( erbB 2 ) leads to amplified heregulin ( HRG ) signaling , promoting more aggressive breast cancer that is nonresponsive to estrogen and the antiestrogenic drug tamoxifen . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Although the mechanism responsible for the differential sensitivity of the various signal transduction pathways to EGFR inhibitors remains unclear , signaling through erbB 2 does not appear to be involved . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Therapeutic blockade of erbB 2 receptor signaling has to date been shown to be effective in only a subset of chemotherapy resistant breast cancer patients . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Identification of patients with transitional cell carcinoma of the bladder overexpressing ErbB 2 , ErbB 3 , or specific ErbB 4 isoforms : real time reverse transcription PCR analysis in estimation of ErbB receptor status from cancer patients . ^^^ Determination of cutoff expression levels indicated tumor specific overexpression of ErbB 2 , ErbB 3 , and specific ErbB 4 isoforms in a subset of TCC patients . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Here we show that cultured tanycytes express erbB 1 and erbB 2 , two of the four members of the erbB receptor family , and respond to TGFalpha with receptor phosphorylation , release of prostaglandin E 2 ( PGE 2 ) , and a PGE 2 dependent increase in the release of TGFbeta 1 , a growth factor previously implicated in the glial control of LHRH secretion . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The heat shock protein 90 inhibitor geldanamycin and the ErbB inhibitor ZD 1839 promote rapid PP 1 phosphatase dependent inactivation of AKT in ErbB 2 overexpressing breast cancer cells . ^^^ AKT , a serine / threonine kinase that promotes cell survival , can be activated by overexpression of the receptor tyrosine kinase ErbB 2 . ^^^ Conversely , down regulation of ErbB 2 inhibits AKT activation . ^^^ Here , we identify PP 1 as a serine / threonine phosphatase that associates with and dephosphorylates AKT in breast cancer cells , and we show that ErbB 2 inhibits PP 1 dependent dephosphorylation of AKT . ^^^ Inhibition of ErbB 2 by either the HSP ( heat shock protein ) 90 inhibitor geldanamycin or the ErbB inhibitor ZD 1839 in SKBR 3 cells , a human breast cancer cell line overexpressing ErbB 2 protein , induces a rapid and dramatic decrease in AKT activity . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
EGFR , ErbB 2 and Ras but not Src suppress RhoB expression while ectopic expression of RhoB antagonizes oncogene mediated transformation . ^^^ In this study , we show that H Ras , N Ras , K Ras , EGFR and ErbB 2 but not 5 Src suppress RhoB promoter transcriptional activity in NIH3T3 cells and human cancer cell lines derived from lung ( A 549 ) , pancreatic ( Panc 1 ) and cervical ( C33A ) tumors . ^^^ The EGFR and ErbB 2 suppression of RhoB promoter activity is mediated by Ras . ^^^ Ectopic expression of RhoB , but not the closely related family member RhoA , antagonizes the ability of EGFR , ErbB 2 , H Ras , N Ras and K Ras but not 5 Src to transform NIH3T3 cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We have found that neuregulin 1beta ( NRG 1beta ) is expressed in the cardiac microvascular endothelium , and promotes the growth and survival of cardiac myocytes in culture through the activation of erbB 2 and erbB 4 receptor tyrosine kinases . ^^^ In contrast , the erbB 2 specific tyrphostin AG 879 had no effect on NRG 1beta activation of Akt . ^^^ Myocyte treatment with an activating antibody to erbB 2 caused phosphorylation of erbB 2 , and led to activation of Erk but not Akt . ^^^ Treatment with the erbB 2 antibody had no effect on anthracycline induced apoptosis . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Androgen receptor versus erbB 1 and erbB 2 expression in human prostate neoplasms . ^^^ Here , we report our work on the measurement of AR mRNA and protein expression in benign prostatic hyperplasia ( BPH ) and prostatic carcinoma ( PCA ) and evaluation of the relationship between AR , erbB 1 and erbB 2 gene expression determined in the same tissue . ^^^ In order to define AR , erbB 1 and erbB 2 in human prostate neoplasms 36 benign prostatic hyperplasia , 46 prostatic carcinoma and 12 normal prostate gland samples were analysed . ^^^ AR , erbB 1 and erbB 2 mRNA expression was estimated by RT PCR . ^^^ The association of AR mRNA and protein expression with erbB 1 and erbB 2 gene expression was evaluated . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The achilles heel of ErbB 2 / HER2 : regulation by the Hsp 90 chaperone machine and potential for pharmacological intervention . ^^^ The chaperone system controls the stability of the nascent forms of both ErbB 1 ( EGF receptor ) and ErbB 2 / HER2 , while regulation of the mature form is restricted to ErbB 2 . ^^^ The importance of an Hsp 90 recognition motif located within the kinase domain of ErbB 2 is discussed , as well as a direct role for Hsp 90 in regulating tyrosine kinase activity . ^^^ In light of recent observations , we emphasize the ability of specific tyrosine kinase inhibitors to selectively target ErbB 2 to the chaperone mediated degradation pathway . ^^^ Hence , the dependence of ErbB 2 upon Hsp 90 reveals an Achilles heel , which opens a window of opportunity for combating cancers driven by the ErbB / HER signaling network . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The epidermal growth factor receptor ( EGFR ) gives name to a family of receptors formed by four members in mammals ( EGFR , ErbB 2 , ErbB 3 , and ErbB 4 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
EGFR and erbB 2 were activated in the vaginal epithelium of mice by estrogen treatment . ^^^ Thus , signal transduction via EGFR and erbB 2 could be related to the estrogen induced vaginal changes and persistent erbBs phosphorylation and sustained expression of EGF like growth factors , leading to ERalpha activation that may result in cancerous lesions in vaginae from neonatally DES exposed mice later in life . . ^^^ EGFR and erbB 2 were activated in the vaginal epithelium of mice by estrogen treatment . ^^^ Immunohistochemical analysis indicated that erbB 2 was primarily expressed in vaginal epithelium . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
MATERIALS AND METHODS : A TMA containing 547 primary HNSCC was used for the analysis of cyclinD 1 , c myc , erbb 1 and erbb 2 expression by immunohistochemistry ( IHC ) . ^^^ RESULTS : CyclinD 1 and c myc were overexpressed at higher frequencies in primary pharyngeal and laryngeal carcinomas compared with primary oral carcinomas ( p < 0 . 001 and p < 0 . 001 ) , while erbb 1 and erbb 2 overexpression was associated with oral site ( p < 0 . 001 and p = 0 . 04 , respectively ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The formation of EGFR and ErbB 2 heterodimers has been recently implicated as an important factor in the induction of sporadic human breast cancers . ^^^ To directly assess whether the catalytic activity of EGFR is required for ErbB 2 induction of mammary tumors , we have interbred transgenic mice expressing ErbB 2 oncogene under the transcriptional control of the mouse mammary tumor virus ( MMTV ) promoter / enhancer to a naturally occurring mouse mutant carrying a catalytically impaired EGFR ( waved 2 mice ) . ^^^ These observations provide evidence that efficient ErbB 2 induced mammary tumor progression requires EGFR dependent activation of Gab1 . . ^^^ Epidermal growth factor receptor dependent activation of Gab 1 is involved in ErbB 2 mediated mammary tumor progression . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
To date , commercially available signal transduction targeting compounds include trastuzumab , a monoclonal antibody against the ErbB 2 receptor for the treatment of metastatic breast cancer overexpressing the ErbB 2 ( HER 2 ) receptor , and gefitinib , an inhibitor of the ErbB 1 receptor tyrosine kinase that recently received regulatory approval for the treatment of patients with non small cell lung cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
A series of 6 alkoxy 4 anilinoquinazoline compounds was prepared and evaluated for in vitro inhibition of the erbB 2 and EGFR kinase activity . ^^^ Further , several of these compounds inhibit the growth of erbB 2 and EGFR over expressing tumor cell lines at concentrations below 1 uM . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Here , general principles for the derivation of cytotoxic proteins and effector cells with antibody dependent tumor specificity are summarized , and current strategies to employ these molecules and cells for directed cancer therapy are discussed , focusing mainly on the tumor associated antigens epidermal growth factor receptor ( EGFR ) and the closely related ErbB 2 ( HER 2 ) as targets . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
It was found that GA depleted EGFR and ErbB 2 in DLD 1 cells and depleted only ErbB 2 in SQ 5 cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NTAK ( neural and thymus derived activator for ErbB kinases ) , also known as neuregulin 2 , is a member of the epidermal growth factor ( EGF ) family , which binds directly to ErbB 3 and ErbB 4 and transactivates ErbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Her 2 / neu ( ErbB 2 ) oncogene , the second member of the epidermal growth factor receptor ( EGFR ) family , encodes a transmembrane tyrosine kinase receptor in Her 2 positive tumors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 2 and erbB 3 receptors , which transduce the NRG 1 signal in Schwann cells , were found throughout the cytoplasm and in the processes and were also localized in the cell nucleus . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In addition , we show that costimulation of ErbB 2 and TGFbeta induces autocrine secretion of factors that are sufficient to induce migration , but not invasion , by means of both epidermal growth factor receptor dependent and independent processes . ^^^ These results support the role of TGFbeta as a pro invasion factor in the progression of breast cancers with activated ErbB 2 and suggest that activation of the Erk and epidermal growth factor receptor pathways are key in mediating these events . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The tyrosine kinase receptor erbB 2 , also known in humans as Her 2 , is a member of the epidermal growth factor receptor ( EGFR or erbB 1 ) family , which also includes erbB 3 and erbB 4 . ^^^ ErbB 2 is expressed in multiple neuronal and non neuronal tissues in embryos and adult animals , including the heart . ^^^ Genetic data demonstrated that erbB 2 is required for normal embryonic development of neural crest derived cranial sensory neurons . ^^^ To study its role at later stages of development , we generated a transgenic mouse line that specifically expresses the rat erbB 2 cDNA in the heart under the control of the cardiac specific alpha myosin heavy chain promoter . ^^^ When crossed into the null background , the expression of the rat erbB 2 cDNA rescued the cardiac phenotype in the erbB 2 null mutant mice that survive until birth but display an absence of Schwann cells and a severe loss of both motor and spinal sensory neurons . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
When erbB 2 monomeric yellow fluorescent protein ( mYFP ) or erbB 3 monomeric Citrine ( mCitrine ) were coexpressed with erbB 1 , the rates and extent of endocytosis of EGF QD and the RTK VFP demonstrated that erbB 2 but not erbB 3 heterodimerizes with erbB 1 after EGF stimulation , thereby modulating EGF induced signaling . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
EXPERIMENTAL DESIGN : We selected three human colon carcinoma cell lines ( LoVo , Caco 2 , which express activated epidermal growth factor receptor and ErbB 2 family members , and SW 620 , which does not ) , and analyzed the effects of CI 1033 both in vitro and in vivo . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In primary hepatocytes , DCA activated ERBB 1 ( the epidermal growth factor receptor ) , ERBB 2 , and the insulin receptor , but not the insulin like growth factor 1 ( IGF 1 ) receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The Neu ( ErbB 2 , HER 2 ) member of the epidermal growth factor receptor family is implicated in many human breast cancers . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Tissue microarrays ( TMAs ) were used to determine the immunohistochemical profile of eight proteins including E cadherin , EGFR , oestrogen and progesterone receptor ( ER and PR ) , MIB 1 , ERBB 2 , MUC 1 , and P 53 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We used the epidermal growth factor ( EGF ) receptor family members ErbB 1 and ErbB 2 as model systems to investigate whether the sugar moiety can be exploited to block signaling by growth factor receptors in human tumor cells ( i . e . , SKBR 3 and A 431 , derived from a breast cancer and a vulval carcinoma , respectively ) . ^^^ The monoclonal anti LeY antibody ABL 364 and its humanized version IGN 311 immunoprecipitated ErbB 1 and ErbB 2 from detergent lysates of A 431 and SKBR 3 , respectively . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
DATA SOURCES : Published articles identified through MEDLINE using search terms such as tyrosine kinase , erbB 1 , erbB 2 , erbB 3 , erbB 4 , epidermal growth factor receptors ( EGFR ) , and EGFR inhibitors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Further , dysregulation of the ErbB network is implicated in a variety of human cancers , and the nature of aberrant signaling through ErbB proteins , as well as current therapeutic approaches , are discussed , highlighting the role of the highly oncogenic ErbB 2 molecule . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Overexpression of ErbB 2 and ErbB 4 receptors in breast cancers may be accompanied by contrasting clinical outcomes . ^^^ Agonistic antibodies were employed to activate ErbB 2 and ErbB 4 in isolation from the other ErbBs in breast cancer cells . ^^^ Our results indicate that , in the same cell line , ErbB 2 and ErbB 4 activation influence gene transcription differentially . ^^^ These include ErbB 4 targets EPS15R , GATA 4 , and RAB 2 and ErbB 2 activated HRY / HES1 and PPAP2A . ^^^ Targets of ErbB 2 homodimer signaling may be especially important as markers in breast cancer , where ErbB 2 homodimerization mediated by overexpression and ligand independent activation is common . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Here we selected the TMs of ErbB 1 and ErbB 2 as a model since these receptors function both as homodimers and as heterodimers . ^^^ We used the ToxR system and expressed the TMs of both ErbB 1 and ErbB 2 containing only the N terminal GXXXG motifs . ^^^ The data revealed that the ErbB 2 but not the ErbB 1 construct formed homodimers . ^^^ Importantly , a synthetic ErbB 1 TM peptide was able to form a heterodimer with ErbB 2 , by displacing the ErbB 2 TM homodimer . ^^^ The specificity of the interaction was demonstrated by using three controls : ( 1 ) Two single mutations within the GXXXG like motif of the ErbB 1 peptide reduced or preserved its activity , in agreement with similar mutations in glycophorin A . ( 2 ) A TM peptide of the bacterial Tar receptor did not assemble with the ErbB 2 construct . ( 3 ) The ErbB 1 peptide had no effect on the dimerization of a construct containing the TM 1 domain of the Tar receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We analyzed a number of cultured ovarian cancer cell lines of different tissue types for the presence or absence of sensitivity to various anticancer drugs as well as expression patterns of oncogene products ( erbB 2 , EGFR , bcl 2 ) . ^^^ Positive correlation between the resistance to anticancer drugs and the oncogene products was obtained by multivariate analysis for ( a ) CDDP and erbB 2 ( b ) 10 p 16 and erbB 2 , and ( c ) MMC and EGFR . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
SK N MC cells expressed multiple NRG 1 proteins and mRNAs encoding several alpha and beta isoforms from the sensory and motor neuron derived factor NRG 1 subfamily as well as the NRG 1 receptor subunits erbB 2 , erbB 3 , and erbB 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
BACKGROUND : Neuregulin is a neuronally derived trophic factor that interacts with erbB 2 and erbB 3 receptors on Schwann cells and is required for normal Schwann cell proliferation , survival , and development . ^^^ METHODS : Pathologic specimens from eight patients undergoing microsurgical removal of vestibular schwannomas and one patient undergoing vestibular nerve section were immunostained with anti neuregulin , anti erbB 2 , anti erbB 3 , and anti phosphorylated erbB 2 antibodies . ^^^ RESULTS : The Scarpa ganglion neurons express neuregulin , and normal vestibular Schwann cells express erbB 2 and erbB 3 . ^^^ Vestibular schwannomas from all eight patients demonstrated neuregulin , erbB 2 , and erbB 3 immunoreactivity . ^^^ In addition , all vestibular schwannomas demonstrated immunoreactivity to anti phosphorylated erbB 2 antibody that only recognizes erbB 2 when it is phosphorylated , or activated . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Recently , 4 studies have shown experimental evidence of a role of the EGFR family , particularly ErbB 2 , in the development of prostate cancer and , more specifically , in the progression to hormone refractory clinical behavior . ^^^ It has been proposed that EGFR family receptors and androgen receptors function synergistically in the absence of androgen suggesting cross talk between the ErbB 2 and androgen receptor pathways , and that mitogen activated protein kinase and phosphatidylinositol 3 kinase can be considered the transduction pathways . ^^^ Finally , clinical trials are currently in progress in patients with prostate cancer testing novel agents that selectively interfere with these receptors , such as trastuzumab , an anti ErbB 2 monoclonal antibody , and gefitinib ( ZD 1839 , Iressa ) , a small molecule selective EGFR tyrosine kinase inhibitor . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Elevated ERBB 2 and epidermal growth factor receptor ( EGFR ) expression levels were detected in ERBB 3 expressing tumors , suggesting the presence of ERBB 3 cognate partners . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Blockade of epidermal growth factor or heregulin dependent ErbB 2 activation with the anti ErbB 2 monoclonal antibody 2C4 has divergent downstream signaling and growth effects . ^^^ We compared the utilization of ErbB 2 in response to epidermal growth factor ( EGF ) and heregulin stimulation in colon carcinoma cells . ^^^ Anti ErbB 2 monoclonal antibody 2C4 blocked heregulin stimulated phosphorylation of ErbB 2 and ErbB 3 ; activation of mitogen activated protein kinase ( MAPK ) , phosphatidylinositol 3 ' kinase ( PI3K ) , and Akt ; proliferation ; and anchorage independent growth . 2C4 blocked EGF mediated phosphorylation of ErbB 2 and inhibited PI3K / Akt and anchorage independent growth but did not affect ErbB 1 or MAPK . ^^^ Furthermore , we identify ErbB 2 as a critical component of EGF signaling to the Gab1 / Gab2 PI3K Akt pathway and anchorage independent growth , but EGF stimulation of MAPK and monolayer growth can occur efficiently without the contribution of ErbB2 . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Our study suggests that residual ErbB 2 activation by EGF , despite EGFR blockade , is responsible for persistent downstream activation of Stat 3 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We excluded any interference with the EGFR , as SK BR 3 cells express considerably lower levels of this receptor , and no detectable EGFR signal was observed by Western blot analysis in the immunoprecipitated ErbB 2 preparations used to perform the overlay assays with biotinylated CaM . ^^^ In the present paper , we show that ErbB 2 could be pulled down using CaM agarose beads in a Ca2+ dependent manner , as detected by Western blot analysis using an anti ErbB 2 antibody . ^^^ ErbB 2 was also isolated by Ca2+ dependent CaM affinity chromatography . ^^^ We also demonstrate using an overlay technique with biotinylated CaM that CaM binds directly to the immunoprecipitated ErbB 2 . ^^^ The binding of biotinylated CaM to ErbB 2 depends strictly on the presence of Ca2+ , since it was prevented by the presence of EGTA . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
To date , most attention has focused on the ErbB 2 receptor . ^^^ Now , in a recent report , it has been shown that ErbB 3 is a critical partner for the transforming activity of ErbB 2 in breast cancer cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We have determined the 3 . 2 A 10 ray crystal structure of the extracellular domain of the human epidermal growth factor receptor 2 ( ErbB 2 or HER 2 ) in a complex with the antigen binding fragment of pertuzumab , an anti ErbB 2 monoclonal antibody also known as 2C4 or Omnitarg . ^^^ Insights into ErbB signaling from the structure of the ErbB 2 pertuzumab complex . ^^^ Pertuzumab binds to ErbB 2 near the center of domain 2 , sterically blocking a binding pocket necessary for receptor dimerization and signaling . ^^^ The ErbB 2 pertuzumab structure , combined with earlier mutagenesis data , defines the pertuzumab residues essential for ErbB 2 interaction . ^^^ To analyze the ErbB 2 side of the interface , we have mutated a number of residues contacting pertuzumab and examined the effects of these mutations on pertuzumab binding and ErbB 2 ErbB3 heterodimerization . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
A new therapeutic antibody masks ErbB 2 to its partners . ^^^ In cancer cells , the ErbB 2 receptor tyrosine kinase can be activated in two ways : by overexpression or by ligand mediated stimulation of another ErbB receptor . ^^^ The ErbB 2 targeting antibody trastuzumab ( Herceptin ) is used for treatment of metastatic breast cancer patients whose tumors overexpress ErbB 2 . ^^^ A new structural study in this issue of Cancer Cell reveals how targeting ErbB 2 with another antibody , pertuzumab ( Omnitarg ) , prevents ligand induced dimerization of ErbB 2 with the other ErbB receptors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
However , mutations within some of these receptors , and recent studies with the epidermal growth factor ( EGF ) and ErbB 2 receptors have indicated that interactions between TM domains do contribute to stabilization of ligand independent and / or ligand induced receptor dimerization and activation . ^^^ To test this hypothesis , we constructed expression vectors encoding short fusion peptides encompassing native or mutated TM domains of the EGF , ErbB 2 , and insulin receptors . ^^^ In human cell lines overexpressing the wild type EGF receptor or ErbB 2 , we observed that the peptides are expressed at the cell surface and that they inhibit specifically the autophosphorylation and signaling pathway of their cognate receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Epidermal growth factor receptor family ( EGFR , ErbB 2 4 ) in gliomas and meningiomas . ^^^ Reports regarding the other EGFR family members , ErbB 2 4 , in brain tumors are sparse . ^^^ In gliomas , quantitative real time reverse transcription ( RT ) PCR revealed the highest EGFR mRNA expression in high grade gliomas , while ErbB 2 and ErbB 3 mRNA were detected only in a few high grade gliomas . ^^^ In meningiomas , quantitative real time RT PCR revealed expression of EGFR , ErbB 2 , and ErbB 4 mRNA in the majority of the tumors . ^^^ Epidermal growth factor receptor family ( EGFR , ErbB 2 4 ) in gliomas and meningiomas . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We will contrast lessons derived from the development of inhibitors of Abl , c Kit , HER2 / neu ( erbB 2 ) , and EGFR , highlight successes and limitations in the field , and propose new approaches for clinical development of tyrosine kinase inhibitor therapy . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Studies on the prostate have shown that ErbB 2 phosphorylation and signaling can be regulated by prostatic acid phosphatase , a histidine acid phosphatase which can dephosphorylate phospho tyrosine residues in the ErbB 2 receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Many of the heterogeneous regions contained genes known to influence the prognosis of cervical cancer , such as 7p ( EGFR ) , 8q ( c MYC ) , 11qcen q 13 ( CCND 1 ) and 17q ( ERBB 2 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In contrast , these responses were unaffected by neutralizing antibodies against other ErbB 1 ligands or the ErbB 2 inhibitors geldanamycin and AG 825 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Cell proliferation , AR , ER alpha , EGFR , ErbB 2 , EGF , IGF 1R , IGF 1 , VEGFR 2 , ERKs 1 and 2 proteins and TGF alpha mRNA , but not ER beta and VEGF , were significantly increased in prostates of TRAMP compared to C57BL / 6 mice . ^^^ Genistein in the diet significantly down regulated cell proliferation , EGFR , IGF 1R , ERK 1 and ERK 2 , but not AR , ER alpha , ER beta , ErbB 2 , EGF , TGF alpha , IGF 1 , VEGF and VEGFR in prostates of TRAMP mice . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 1 and ErbB 2 are overexpressed in a wide variety of tumors including breast , colorectal , ovarian , and non small cell lung cancers . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Expression of fatty acid synthase , ErbB 2 and Ki 67 in head and neck squamous cell carcinoma . ^^^ ErbB 2 ( Her 2 / neu ) , a transmembrane tyrosine kinase member of the ErbB receptor family , is known to be overexpressed in a variety of tumors and was recently shown to regulate FAS production in breast epithelial cell lines . ^^^ Herein we analyzed by immunohistochemistry the expression of FAS , ErbB 2 , and the proliferation marker Ki 67 in 62 head and neck squamous cell carcinoma ( HNSCC ) samples . ^^^ Approximately 78 % of the cases were positive for FAS or ErbB 2 at the cell membrane and 70 % of the tumors that showed a high expression of FAS were also strongly positive for ErbB 2 ( Fisher ' s exact test , p = 0 . 01 ) . ^^^ The immunolabeling for both FAS and ErbB 2 was stronger in histologically well differentiated lesions . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Finally , our findings support the notion that most EGFr are excluded from GEM , while an important fraction of ErbB 2 is found to be associated with these microdomains in membranes from CHO K 1 cells . . ^^^ We also explored the endogenous expression , in wild type CHO K 1 cells , of the orphan receptor ErbB 2 ( which is the preferred heteroassociation partner of all other ErbB proteins ) and the effect of GD 3 expression on its membrane distribution . ^^^ Our results showed that CHO K 1 cells endogenously express ErbB 2 and that expression of the GD 3 affected , to some extent , the membrane distribution of endogenous ErbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Selected cut off points for p 185 ( erbB 2 ) and EGFR membrane appear to have good discriminating power to differentiate control tissues versus uninvolved tissues from patients with lung cancer ( AUC = 89 % and 90 % , respectively ) ; while AUC increased to at least 90 % for selected cut off points for p 185 ( erbB 2 ) membrane , EGFR membrane , and FASE when comparing between control versus carcinoma tissues from lung cancer cases . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Akt activation was blocked by wortmannin and LY 294 , 002 , two inhibitors of PI 3 K ; by genistein , a protein tyrosine kinase inhibitor and an ER agonist ; by AG 825 , a selective ErbB 2 inhibitor ; and by the antiestrogens ICI 182 , 780 and 4 hydroxy tamoxifen ; but not by rapamycin , an inhibitor of the ribosomal protein kinase p70S6K ; nor by AG 30 , a selective epidermal growth factor receptor inhibitor . ^^^ Estradiol rapidly activates Akt via the ErbB 2 signaling pathway . ^^^ In this report we now show that estradiol can also rapidly activate phosphatidylinositol 3 kinase ( PI 3 K ) / Akt and that this effect is mediated by the ErbB 2 signaling pathway . ^^^ Estradiol did not activate Akt in MCF 7 cells stably transfected with an anti ErbB 2 targeted ribozyme , further confirming a role for ErbB 2 . ^^^ Taken together , our data suggest that estradiol , bound to membrane ERalpha , interacts with and activates an ErbB dimer containing ErbB 2 , inducing activation of PI 3 K / Akt . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB family members , such as epidermal growth factor receptor 1 ( erbB 1 ) , erbB 2 , erbB 3 and erbB 4 , are widely distributed in organ tissues , and these receptors are suspected tumorigenesis factors . ^^^ ErbB family members , such as epidermal growth factor receptor 1 ( erbB 1 ) , erbB 2 , erbB 3 and erbB 4 , are widely distributed in organ tissues , and these receptors are suspected tumorigenesis factors . ^^^ ErbB 2 is associated with aggressive cancers and is used as a biological marker for the disease ; Northern blot and reverse transcription polymerase chain reaction ( RT PCR ) analyses have shown it to be increased in Graves ' disease . ^^^ Additional studies indicated a similar result in papillary carcinoma cells ; mRNAs of erbB 2 and erbB 3 were increased but erbB 4 mRNA was decreased , suggesting distorted erbB expression may be associated with tumorigenesis . ^^^ However , only erbB 2 overexpression is associated with Graves ' disease . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Identification of a small peptide that inhibits the phosphorylation of ErbB 2 and proliferation of ErbB 2 overexpressing breast cancer cells . ^^^ ErbB 2 is overexpressed in approximately 30 % of breast cancer patients with a correlation to poor prognosis . ^^^ ErbB 2 has been identified as a useful receptor for molecular targeting . ^^^ The library was panned against 2 different purified forms of the external domain of ErbB 2 . ^^^ This resulted in the identification of several ErbB 2 binding phage clones with variable binding to different ErbB 2 preparations . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
To examine the role of ErbB 4 in neuron migration , we cloned and stably transfected each of the four ErbB 4 isoforms in ST14A cells ( a neural progenitor cell line derived from the striatum of embryonic day 14 rats ) endogenously expressing the other members of the ErbB family : ErbB 1 , ErbB 2 , and ErbB 3 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
A recombinant human NGC extracellular domain induced tyrosine phosphorylation of ErbB 2 and ErbB 3 as well as cell growth of the human breast tumor cell lines , T47D and MDA MB 453 . ^^^ In vitro pull down assay revealed that NGC could directly bind to a recombinant ErbB 3 immunoglobulin Fc fusion protein ( ErbB 3 Fc ) but not to ErbB 1 Fc , ErbB 2 Fc or ErbB 4 Fc . ^^^ Taken together , these data indicate that NGC is an active growth factor and a direct ligand for ErbB 3 and that NGC transactivates ErbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In the present study the authors evaluated the expression of the EGFR family members ErbB 2 4 in renal cell carcinoma ( RCC ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
B82L cells lack epidermal growth factor receptor ( EGFR ) but express LPA ( 1 3 ) , platelet derived growth factor ( PDGF ) , ErbB 2 , and insulin like growth factor receptor transcripts , yet LPA caused no detectable transphosphorylation of these receptor tyrosine kinases . ^^^ LPA induced transphosphorylation of the EGFR , ErbB 2 , or PDGF receptor was not required for its antiapoptotic effect . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We examined SIRPalpha 1 regulation in U87MG and U373MG cells in comparison with clonal derivatives that express a truncated form of erbB 2 , which negatively regulates EGFR signaling by inducing the formation of nonfunctional heterodimeric complexes . ^^^ Interestingly , pharmacological inhibition of the kinase activities of EGFR , erbB 2 , and src and activation of mitogen activated protein kinase , but not phosphatidylinositol 3 ' kinase , significantly up regulated SIRPalpha 1 promoter activity . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The neu ( c erbB 2 or HER 2 ) proto oncogene which encodes a receptor protein homologous to the epidermal growth factor receptor is overexpressed in 20 % 30 % of human breast and ovarian cancers . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 2 and EGFR are attractive oncology therapeutic targets as their overexpression in tumors predicts a poorer clinical outcome in a variety of epithelial malignancies . ^^^ A comparison of expression or phosphorylation of these markers with patient outcome revealed that response to Herceptin depended not only on expression levels of erbB 2 but also on expression of EGFR , expression of erbB ligands , expression of other receptors and phosphorylation of downstream proteins . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Here we tested whether the related human LRIG 1 ( also called Lig 1 ) protein can act as a negative regulator of EGF receptor and its relatives , ErbB 2 , ErbB 3 , and ErbB 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
To test this hypothesis , we examined the expression of the NRG 1 receptor subunits erbB 2 , erbB 3 , and erbB 4 in rat lumbar DRG and spinal cord . ^^^ Virtually all DRG neurons are erbB 2 and erbB 3 immunoreactive , with erbB 4 also detectable in many neurons . ^^^ In spinal cord white matter , erbB 2 and erbB 4 antibodies produce dense punctate staining , whereas the erbB 3 antibody primarily labels glial cell bodies . ^^^ Spinal cord dorsal and ventral horn neurons , including alpha motor neurons , exhibit erbB 2 , erbB 3 , and erbB 4 immunoreactivity . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Alterations of chromosomes ( 3p , 5q , 9p ) , genes ( Rb , C myc , C mos , hTERT ) , proteins ( p 16 , p 53 , K ras , hnRNP A2 / B1 , MCM 2 , EGFR , erbB 2 , erbB 3 , erbB 4 ) and others can be found in lung cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Neuregulin ( NRG ) is a heparin binding factor that activates members of the epidermal growth factor family of tyrosine kinase receptors including erbB 2 that is overexpressed in more aggressive types of breast cancer . ^^^ As the cells progress to malignancy , they expressed higher levels of erbB 2 and lower levels of erbB 3 and secreted high levels of NRG into the culture media , resulting in high basal levels of erbB receptor phosphorylation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We found that NRG 1 is expressed by spiral ganglion neurons ( SGNs ) , whereas erbB 2 and erbB 3 are expressed by supporting cells of the organ of Corti , suggesting that these molecules mediate interactions between these cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In an effort to elucidate the role of ErbB receptors in human head and neck squamous cell carcinoma ( HNSCC ) , expression abnormalities and subcellular localization of epidermal growth factor receptor ( EGFR ) , ErbB 2 , ErbB 3 , and ErbB 4 were investigated along with EGF and tenascin by immunohistochemistry in 38 carcinomas as compared to adjacent normal mucosa of 24 cases . ^^^ Although tumour specific overexpression affected each ErbB receptor ( EGFR 47 % , ErbB 2 29 % , ErbB 3 21 % , ErbB 4 26 % ) , EGFR abnormalities were most prevalent . ^^^ In spite of frequent ErbB receptor alterations , autologous ErbB serum antibodies were rare , with only 1 of 38 tumour patients exhibiting an ErbB 2 specific immune response . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
GW 572016 ( Lapatinib ) is a tyrosine kinase inhibitor in clinical development for cancer that is a potent dual inhibitor of epidermal growth factor receptor ( EGFR , ErbB 1 ) and ErbB 2 . ^^^ Surprisingly , we found that GW 572016 has a very slow off rate from the purified intracellular domains of EGFR and ErbB 2 compared with OSI 774 and another EGFR selective inhibitor , ZD 1839 ( Iressa ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
It also inhibited signal transduction in heregulin stimulated breast tumour cells , indicating that it does not only block EGFR but also its closely related erbB 2 gene product . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Next , we analyzed expression levels of phosphorylated ERK1 / 2 and compared these results with EGFR ( HER 1 / ErbB1 ) and HER2 / neu ( ErbB 2 ) expression levels , as EGFR conducts signals through Ras Raf MAPK pathway ; gefitinib inhibited phosphorylation of ERK1 / 2 by EGF addition in cell lines with detectable and undetectable EGFR expression . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The other three genes coding for the ErbB receptors did not present point mutations , or rearrangements , and only a very low amplification rate was found for erbB 2 ( 1 case ) and erbB 3 ( 4 cases ) . ^^^ No overexpression of erbB 2 , erbB 3 or erbB 4 was detected . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Recent structural studies of ErbB 2 in complex with anti ErbB 2 antibodies ( trastuzumab / Herceptin and pertuzumab / Omnitarg ) have provided significant insights into how these drugs function . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Over the past year , the field has progressed from having a complete absence of 10 ray crystal structures to having eight such structures ; ErbB 2 alone or complexed with the two monoclonal antibodies pertuzumab ( Genentech Inc / Roche Holdings AG / Chugai Pharmaceutical Co Ltd ) and trastuzamab , ErbB 3 without a ligand , EGFR with a ligand bound in an unactivated monomeric conformation , and EGFR with either epidermal growth factor ( EGF ) or transforming growth factor alpha ( TGFalpha ) in a 2 : 2 dimeric complex . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The ErbB 2 gene product is a transmembrane glycoprotein belonging to the epidermal growth factor receptor family , and its cytoplasmic domain is responsible for sending the mitogenic signals into cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
RESULTS : We demonstrated that CM ( Coll ) Listeria / TSB increases the tyrosine phosphorylation level of ErbB 2 and ErbB 3 , members of the epidermal growth factor receptor ( EGFR ) family , and the association between ErbB 3 and the phosphatidylinositol 3 kinase ( PI3K ) regulatory subunit ( p85alpha ) . ^^^ CM ( Coll ) Listeria / TSB stimulated ErbB 3 tyrosine phosphorylation and cancer cell invasion were independent from EGFR expression and activity but dependent on ErbB 2 activity . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Stimulation of the duct cells with epidermal growth factor ( EGF ) and betacellulin results in Tyr phosphorylation of ErbB 1 and ErbB 2 , followed by activation of Shc , MEK1 / 2 and ERK1 / 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NRG 1beta effects on neurite extension and arborization are similar to , but not additive with , those of brain derived neurotrophic factor and reflect direct NRG 1 action on hippocampal neurons as these cells express the NRG 1 receptors erbB 2 and erbB 4 , the erbB specific inhibitor PD 158780 decreases NRG 1beta induced neurite outgrowth , and NRG 1beta stimulation induces p42 / 44 ERK phosphorylation . ^^^ We conclude that NRG 1beta stimulates hippocampal neurite extension and arborization via a signaling pathway that involves erbB membrane tyrosine kinases ( erbB 2 and / or erbB 4 ) , p42 / 44 ERK , and PKC . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : Human corneal epithelial cells ( HCECs ) were functionally depleted of erbB 2 to elucidate its role in epidermal growth factor ( EGF ) receptor ( EGFR ) activation dependent cell migration . ^^^ Role of ErbB 2 in Corneal Epithelial Wound Healing . ^^^ METHODS : The retrovirus pBabe 5R , which encodes an erbB 2 single chain antibody with an endoplasmic reticulum ( ER ) targeting sequence , and control pBabe puro were used to infect THCE cells ( an SV 40 immortalized HCEC line ) . ^^^ The depletion of erbB 2 was verified by cell surface biotinylation of proteins , followed by streptavidin precipitation and subsequent detection of erbB 2 by immunoblot analysis . ^^^ Activation of erbBs was analyzed by immunoprecipitation using the phosphotyrosine antibody pY 20 , followed by Western blot analysis with erbB 1 or erbB 2 antibodies . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
METHODS : Bronchial biopsies obtained from non smokers ( n = 10 ) and current smokers , with or without chronic obstructive pulmonary disease ( n = 51 ) , were examined immunohistochemically to measure the expression of epidermal growth factor receptor , ErbB 2 , ErbB 3 , ErbB 4 and mucin subtypes ( MUC 2 , MUC5AC and MUC5B ) in the bronchial epithelium . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Hsp 90 restrains ErbB 2 / HER2 signalling by limiting heterodimer formation . ^^^ ErbB 2 / HER2 is an oncogenic tyrosine kinase that regulates a signalling network by forming ligand induced heterodimers with several growth factor receptors of the ErbB family . ^^^ Hsp 90 and co chaperones regulate degradation of ErbB 2 but not other ErbB members . ^^^ The capacity of ErbB 2 to recruit ligand bound receptors into active heterodimers is limited by Hsp 90 , which is dissociated from ErbB 2 following ligand induced heterodimerization . ^^^ We show that Hsp 90 binds a specific loop within the kinase domain of ErbB 2 , thereby restraining heterodimer formation and catalytic function . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The erbB receptor family ( EGFr , erbB 2 , erbB 3 , and erbB 4 ) consists of transmembrane glycoproteins that transduce extracellular signals to the nucleus when activated . erbB family members are widely expressed in epithelial , mesenchymal , and neuronal cells and contribute to the proliferation , differentiation , migration , and survival of these cell types . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We studied the binding of the peptides from epidermal growth factor receptor ( EGFR ) and its homolog ( ErbB 2 ) , corresponding to their autophosphorylation sites , to PAP using theoretical modeling and molecular dynamics ( MD ) simulation methods . ^^^ Thus we demonstarted that PAP could potentially bind to EGFR and Erbb 2 and dephosphorylate them . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Moreover , alpha6beta4 associated haptotaxis inhibition was linked to a phosphatidylinositol 3 kinase ( PI3K ) pathway and required erbB 2 activation . erbB 2 , the ligand less member of the epidermal growth factor receptor family , was shown to form a complex with the hemidesmosomal integrin alpha6beta4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 2 , an epidermal growth factor receptor family member whose overexpression in mammary tumors is correlated with poor patient prognosis , has been implicated as a positive modulator of VEGF expression . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
HER 2 ( human epidermal growth factor receptor 2 ; also known as erbB 2 ) and its relatives HER 1 ( epidermal growth factor receptor ; EGFR ) , HER 3 and HER 4 belong to the HER family of receptor tyrosine kinases . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
MIA PaCa 2 and BxPC 3 protein lysates were probed with antibodies to EGFR , ErbB 2 , ErbB 3 , and ErbB 4 . ^^^ Although both cell lines expressed EGFR and ErbB 2 protein , ErbB 3 protein was selectively expressed by BxPC 3 cells , where it also showed evidence of constitutive phosphorylation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Overexpression of the erbB 2 receptor occurs in 20 30 % of all breast cancers , and seems to be involved in chemotherapeutic resistance of breast cancer cells and radioresistance of lung cancer cells . ^^^ The hypothesis of this study was that erbB 2 confers resistance to radiation induced apoptosis in breast cancer cells through the phosphatidylinositol 3 kinase ( PI 3 K ) / Akt signalling pathway . ^^^ BT 474 cells overexpress erbB 2 and have mutated p 53 , while MCF 7 have normal expression of erbB 2 and functional p 53 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Molecular modeling of nearly full length ErbB 2 receptor . ^^^ To facilitate the understanding of receptor structure and function at the molecular level , a molecular model was built for the nearly full length ErbB 2 dimer . ^^^ Favorable dimerization interactions are predicted for the extracellular , transmembrane , and protein kinase domains in the model of a nearly full length dimer of ErbB 2 , which may act in a coordinated fashion in ErbB 2 homodimerization , and also in heterodimers of ErbB 2 with other members of the ErbB family . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB receptors associate in a ligand dependent or independent manner , and overexpression of epidermal growth factor receptor ( ErbB 1 ) or ErbB 2 results in ligand independent activation . ^^^ ErbB receptors associate in a ligand dependent or independent manner , and overexpression of epidermal growth factor receptor ( ErbB 1 ) or ErbB 2 results in ligand independent activation . ^^^ In contrast , ligand binding facilitates heterodimerization with ErbB 2 and is expected to stabilize an extended conformation of the ErbB 3 extracellular domain ( ECD ) in which the dimerization interface is exposed . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Unlike other ErbB proteins , ErbB 2 binds no known EGF like ligand . ^^^ To address the existence of a direct ligand for ErbB 2 , we applied algorithms based on genomic and cDNA structures to search sequence data bases . ^^^ A recombinant EPG can not stimulate cells singly expressing ErbB 2 , but it acts as a mitogen for cells expressing ErbB 1 and co expressing ErbB 2 in combination with the other ErbBs . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Neuregulin receptor ErbB 2 localization at T tubule in cardiac and skeletal muscle . ^^^ Recent reports indicate that breast cancer therapy with humanized monoclonal ErbB 2 antibody induces cardiomyopathy , suggesting that ErbB 2 serves as a crucial signaling receptor , even in the adult heart . ^^^ Here , we examine ErbB 2 expression and localization in both cardiac and skeletal muscle of adult mice via immunoblot and immunohistochemistry . ^^^ ErbB 2 was detected as a band approximately 185 kD molecular mass in each cardiac and skeletal muscle extraction . ^^^ Confocal images of double labeling showed that ErbB 2 was colocalized with caveolin 3 in cardiac muscle and with dihydropyridine receptor in skeletal muscle , suggesting that ErbB 2 was localized at the T tubule . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The issue of the association between ErbB 2 expression and gefitinib activity was addressed , while clinical data of a phase 2 study of gefitinib in advanced breast cancer were presented . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Antiestrogen resistant breast cancers often show increased expression of the epidermal growth factor receptor family members , ErbB 1 and ErbB 2 . ^^^ ErbB 2 or ErbB 1 overexpression can abrogate tamoxifen sensitivity in breast cancer lines through both reduction in p 27 levels and inhibition of its function . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
H 1819 , a NSCLC cell line that expresses high levels of EGFR , ErbB 2 , and ErbB 3 but has wild type EGFR , showed intermediate sensitivity to TKIs . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
This study was performed to clarify and compare the expressions of EGFR , erbB 2 and MMP 9 in hepatolithiasis and cholangiocarcinoma . ^^^ The expressions of EGFR , erbB 2 and MMP 9 in tissue samples were examined by immunohistochemistry using respective monoclonal antibodies . ^^^ RESULTS : In traumatic livers , the expressions of EGFR , erbB 2 and MMP 9 were all negative . ^^^ Expression of epidermal growth factor receptor , ErbB 2 and matrix metalloproteinase 9 in hepatolithiasis and cholangiocarcinoma ] . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The ErbB family , ErbB 1 ( also known as the epidermal growth factor receptor EGFR ) , ErbB 2 , ErbB 3 , and ErbB 4 comprise a group of receptor tyrosine kinases that interact with ligands from the epidermal growth factor ( EGF ) superfamily , subsequently dimerize , catalytically activate each other by cross phosphorylation , and then stimulate various signaling pathways . ^^^ EGFR , ErbB 2 , and ErbB 4 exhibited distinct but sometimes overlapping distributions in multiple cell types within germinal zones , cortex , striatum , and hippocampus in prenatal and postnatal development . ^^^ EGFR , ErbB 2 , and ErbB 4 exhibited distinct but sometimes overlapping distributions in multiple cell types within germinal zones , cortex , striatum , and hippocampus in prenatal and postnatal development . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Other studies also correlate EGF receptor ( EGFR ) expression with poor prognosis in breast cancer , but follow up studies suggest that this association is much less robust than with ErbB 2 , and requires more careful analysis . ^^^ ErbB2 / HER2 / Neu can be activated by simple overexpression , and its signaling is thought to play an important role in initiation and progression of ErbB 2 positive breast cancers . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Study of the biologic effects of lapatinib , a reversible inhibitor of ErbB 1 and ErbB 2 tyrosine kinases , on tumor growth and survival pathways in patients with advanced malignancies . ^^^ PURPOSE : This was a pilot study to assess the biologic effects of lapatinib on various tumor growth / survival pathways in patients with advanced ErbB 1 and / or ErbB 2 overexpressing solid malignancies . ^^^ PATIENTS AND METHODS : Heavily pretreated patients with metastatic cancers overexpressing ErbB 2 and / or expressing ErbB 1 were randomly assigned to one of five dose cohorts of lapatinib ( GW 572016 ) administered orally once daily continuously . ^^^ Responders exhibited variable levels of inhibition of p ErbB 1 , p ErbB 2 , p Erk1 / 2 , p Akt , cyclin D 1 , and transforming growth factor alpha . ^^^ CONCLUSION : Lapatinib exhibited preliminary evidence of biologic and clinical activity in ErbB 1 and / or ErbB 2 overexpressing tumors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Neuregulin receptors erbB 2 and erbB 4 in failing human myocardium depressed expression and attenuated activation . ^^^ In cultured cardiomyocytes , erbB 2 and erbB 4 receptors regulate apoptosis by controlling bcl 10 splicing , and conditional elimination of erbB 2 induces dilative cardiomyopathy in vivo . ^^^ ErbB receptors , expressed in cardiomyocytes and noncardiomyocytes , are downregulated in failing myocardium as mRNA ( which is renormalized by hemodynamic unloading ) and as protein ( erbB 2 : 25 % ; erbB 4 : 70 % ) , their phosphorylation is reduced and bcl 10 splicing is shifted towards 6 . 7 fold augmentation of proapoptotic Bcl xS , compatible with attenuated erbB signaling . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
HER2 / ErbB 2 belongs to a family of four receptors that bind growth factors as dimers and transmit cellular signals . ^^^ The ErbB 2 signaling unit shares functional characteristics with other modules whose function is essential for morphogenesis of epithelial organs , including the mammary gland . ^^^ However , unlike other receptors , ErbB 2 binds no known growth factor ligand with high affinity , and its oncogenic potential is exceptionally high . ^^^ Biochemical and genetic lines of evidence imply that ErbB 2 is a unique receptor : by serving as a preferred heterodimeric partner of the other ErbB receptors , it enhances and prolongs cell to cell signals . ^^^ ErbB 2 containing heterodimers are long lived and their signals are relatively potent because the rate of ligand dissociation is decelerated by ErbB 2 , and their rate of endocytosis is relatively slow . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Metastases in breast cancer are a vital concern in treatment , with epidermal growth factor receptor and ErbB 2 strongly implicated in mediating tumor invasion and spreading . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
EGF R and erbB 2 in murine tooth development after ethanol exposure . ^^^ Epidermal growth factor receptor type 1 ( EGF R ) and epidermal growth factor receptor type 2 ( erbB 2 ) immunoexpression during the lower first molar morphogenesis was investigated in mouse fetuses exposed to ethanol during gestation . ^^^ Immunohistochemistry was applied to EGF R and erbB 2 . ^^^ RESULTS : At days 16 . 5 and 18 . 5 , fetuses from 15 % , 20 % , and 25 % ethanol groups showed delayed differentiation , degenerative changes in dental epithelial tissues and reduced dental size ; additionally , they displayed an enhanced immunoreactivity to EGF R and erbB 2 . ^^^ Epidermal growth factor receptor type 1 ( EGF R ) and epidermal growth factor receptor type 2 ( erbB 2 ) immunoexpression during the lower first molar morphogenesis was investigated in mouse fetuses exposed to ethanol during gestation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Decreased accessibility and lack of activation of ErbB 2 in JIMT 1 , a herceptin resistant , MUC 4 expressing breast cancer cell line . ^^^ Overexpression of erbB 2 in breast tumors is associated with poor prognosis and is a target of receptor oriented cancer therapy . ^^^ Trastuzumab ( Herceptin ) , a monoclonal antibody against a membrane proximal epitope in the extracellular region of erbB 2 , shows a therapeutic effect against a fraction of erbB 2 amplified breast tumors . ^^^ Here we investigated the properties of erbB 2 in a Herceptin resistant cell line , JIMT 1 , established from a breast cancer patient showing erbB 2 gene amplification and primary resistance to Herceptin . ^^^ The expression profile of erbB proteins , Herceptin induced erbB 2 internalization , and down regulation in JIMT 1 were similar to those in Herceptin sensitive lines . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The Epidermal Growth Factor Receptor ( EGFR ) and its structural relative erbB 2 are frequently over expressed in ovarian cancers and both are strongly associated with poor patient survival . ^^^ The extent of TGF alpha stimulated migration on collagen in these assays could be associated with erbB 2 expression levels . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Here , we demonstrate that ErbB 2 , ErbB 3 and ErbB 4 are expressed in cultured human melanocytes . ^^^ Western analyses with receptor specific antisera revealed protein bands with Mr values of 185 and 160 kDa , corresponding to ErbB 2 and ErbB 3 , respectively . ^^^ Two malignant melanoma cell lines expressed ErbB 2 and ErbB 3 , but not the full length ErbB 4 receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Other putative factors include proliferative rate , the presence of lymphatic or vascular invasion , human epidermal growth factor receptor 2 ( HER 2 / neu or erbB 2 ) positivity , the presence of micrometastases in lymph nodes or bone marrow , and gene expression profile by microarray analysis , and by RNA based methodology . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 1 and ErbB 2 were located in basal and lateral membranes of acinar and ductal cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
During chemotherapy with anthracyclines , attenuated neuregulin signaling by the erbB 2 receptor inactivating antibody Trastuzumab enhances the heart failure risk . ^^^ Attenuating erbB signals in cultured neonatal rat cardiomyocytes by the erbB 2 antagonist tyrphostin AG 825 , by the erbB1 / 4 antagonist AG 1478 or by antisense induced lowering of erbB 2 receptors resulted in an augmented Bcl xS / Bcl xL ratio , mitochondrial release of cytochrome c , activation of caspase 9 and caspase 3 , and nucleosome sized DNA fragmentation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We also found that arsenite stimulated EGF ( ErbB 1 ) and ErbB 2 receptor transactivation , manifest as receptor tyrosine phosphorylation , appeared to be a proximal signaling event leading to p21Cip1 / Waf1 induction , because both pharmacological inhibitors and knockdown of receptors by RNA interference blocked arsenite induced p21Cip1 / Waf1 upregulation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 1 and ErbB 2 receptors are well characterized targets for anticancer drugs , but the clinical relevance of the related ErbB 4 receptor is unknown . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
YB 1 transduced cells overexpressed EGFR , but ErbB 2 ( Her 2 / neu ) levels were unchanged . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
An overexpression of sox 2 , sox 10 , pax 6 , fzd , erbB 2 , and erbB 4 is found in nestin positive MSCs . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
HER 2 ( also known as NEU , EGFR 2 , or ERBB 2 ) is a member of the EGFR family of receptor tyrosine kinases and plays important roles in the pathogenesis of certain human cancers , and mutations have recently been reported in lung cancers . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Greater letrozole responses were associated with high and low levels of estrogen receptor expression and with coexpression of ErbB 1 and / or ErbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Phosphorylation of both EGFR and ErbB 2 is a reliable predictor of prostate cancer cell proliferation in response to EGF . ^^^ ErbB 2 recruitment potentiated EGF induced signals and was associated with the most pronounced effects of EGF despite low EGFR expression . ^^^ In this way , the sum of EGFR and ErbB 2 receptor phosphorylation proved to be a more sensitive indicator of EGF induced proliferation than quantification of the expression of either receptor alone . ^^^ Extrapolation of these findings to clinical PC suggests that assessment of phosphorylated EGFR + ErbB 2 together could serve as a marker for sensitivity to anti EGFR targeted therapies . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The hazard risk for metastasis development in stage I / II disease was increased at least 3 fold for tumors with high expression levels of insulin receptor , neurotrophic tyrosine receptor kinase 1 , epidermal growth factor receptor , ERBB 2 , ERBB 3 , platelet derived growth factor receptor beta , fibroblast growth factor receptor 1 , or leukocyte tyrosine kinase . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Akt phosphorylation was blocked by inhibitors of phosphatidylinositol 3 kinase ( PI 3 K ) , by antiestrogens , the protein tyrosine kinase inhibitor , genistein , and by AG 825 , a selective ErbB 2 inhibitor ; but not by AG 30 , a selective EGFR inhibitor . ^^^ Experiments employing selective ErbB inhibitors demonstrate that the effect of HRG beta 1 on ER alpha expression and activity is also mediated by ErbB 2 and not by EGFR , demonstrating that ErbB 2 is the primary mediator of the effects of HRG beta 1 on ER alpha regulation . ^^^ This study examines whether the serine / threonine protein kinase , Akt , is involved in the crosstalk between the ErbB 2 and estrogen receptor alpha ( ER alpha ) pathways . ^^^ HRG beta 1 did not activate Akt in MCF 7 cells stably transfected with an anti ErbB 2 targeted ribozyme , further confirming a role for ErbB 2 . ^^^ Taken together , our data suggest that HRG beta 1 , bound to the ErbB 2 ErbB3 heterodimer , in the presence of membrane ER alpha , interacts with and activates PI 3 K / Akt . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In the current study , the authors analyzed the expression of epidermal growth factor receptor ( EGFR ) , ERBB 2 , and KIT in 281 patients with STS who were treated in a single institution . ^^^ Expression was assessed using immunohistochemical stains for EGFR , ERBB 2 , and KIT on formalin fixed , paraffin embedded tissue sections by standard avidin biotin peroxidase complex technique and EGFR detection system . ^^^ Expression of epidermal growth factor receptor , ERBB 2 and KIT in adult soft tissue sarcomas : a clinicopathologic study of 281 cases . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
RESULTS : In genetic screens for mutants with disruptions in myelinated nerves , we identified mutations in erbb 3 and erbb 2 , which together encode a heteromeric tyrosine kinase receptor for Neuregulin ligands . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Agents targeting BCR ABL ( imatinib mesylate [ formerly known as STI 571 ] , Gleevec ; Novartis Pharmaceuticals Corp , East Hanover , NJ ) , retinoid receptor fusion proteins ( all trans retinoic acid ) , ErbB 2 or HER2 / neu ( trastuzumab , Herceptin ; Genentech , Inc , South San Francisco , CA ) , epidermal growth factor receptor ( IMC C 225 and ZD 1839 ) , and the phosphatidylinositol 3 kinase pathway ( CCI 779 ) have all induced remarkable , nontoxic responses in a subset of patients with cancer and abnormalities in the corresponding signal transduction cascades . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Herceptin was found to blunt proliferation of SKBr 3 cells overexpressing EGFR , ErbB 2 , and ErbB 3 and expressing functional PTEN , probably by recruiting PTEN to the plasma membrane . ^^^ Akt was found to be constitutively phosphorylated both in SKBr 3 cells overexpressing EGFR , ErbB 2 and ErbB 3 , and in SKOv 3 cells , overexpressing EGFR and ErbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
LV protein levels of NRG 1 , erbB 2 , and erbB 4 receptors were similar in WT Dox and NRG 1 ( + / ) Dox mice . ^^^ However , levels of phosphorylated erbB 2 , Akt , and ERK 1 / 2 were significantly decreased in NRG 1 ( + / ) Dox compared with WT Dox mice . ^^^ This is associated with the depression of activation of the erbB 2 receptor as well as Akt , p70S6K , and ERK 1 / 2 pathways . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Likewise we determined the cytosolic levels of cathepsin D and tissue type plasminogen activator ( t PA ) , as well as the concentrations of the epidermal growth factor receptor ( EGFR ) , erbB 2 oncoprotein , CD44v5 and CD44v6 on cell surfaces . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We standardized the newly developed protocol using erbB 2 overexpressing SKBR 3 breast cancer cells and compared the results with conventional protocols employing about 10 times more plate adhered fixed or live cells . ^^^ Some of the clones from each biopanning protocol bound to purified erbB 2 and shared motifs with erbB family of receptors and their known ligands . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Tgfbr 2 ( fspKO ) mammary fibroblasts transplanted with mammary carcinoma cells promote growth and invasion , which is associated with increased activating phosphorylation of the receptors : erbB 1 , erbB 2 , RON , and c Met . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Loss of RALT / MIG 6 expression in ERBB 2 amplified breast carcinomas enhances ErbB 2 oncogenic potency and favors resistance to Herceptin . ^^^ Although mutational inactivation of the RALT gene was not detected in human breast carcinomas , RALT mRNA and protein expression was strongly and selectively reduced in ERBB 2 amplified breast cancer cell lines . ^^^ Reconstitution of RALT expression in ERBB 2 amplified SKBr 3 and BT 474 cells inhibited ErbB 2 dependent mitogenic signalling and counteracted the ability of ErbB ligands to promote resistance to the ErbB 2 targeting drug Herceptin . ^^^ Thus , loss of RALT expression cooperates with ERBB 2 gene amplification to drive full oncogenic signalling by the ErbB 2 receptor . ^^^ Moreover , loss of RALT signalling may adversely affect tumor responses to ErbB 2 targeting agents . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Using antibodies specific for the erbB receptors , we demonstrate the expression patterns for the erbB 2 , erbB 3 , and erbB 4 receptors in human glioma biopsy samples . ^^^ Next , we investigate the status of the erbB 2 and erbB 3 receptors in the human glioma cell lines and find that they are constitutively tyrosine phosphorylated and heterodimerized . ^^^ Furthermore , we show that exogenous activation of erbB 2 and erbB 3 receptors in U 251 glioma cells by recombinant Nrg 1beta results in enhanced glioma cell growth under conditions of serum deprivation . ^^^ This enhancement is due to an increase in cell survival rather than an increase in cell proliferation and is dependent on the activation of erbB 2 and phosphatidylinositol 3 kinase ( PI3K ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB family of receptors include 4 different receptors , each of which , with the exception of ErbB 2 , has a number of ligands . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The expression of EGF receptors ( ErbB 1 and ErbB 2 , but not ErbB 3 or ErbB 4 ) was down regulated significantly in the same forebrain regions . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Deregulated signaling of ErbB 2 receptor tyrosine kinase is often associated with hormone resistance in estrogen receptor alpha ( ERalpha ) positive breast cancers , establishing a relationship between ErbB 2 and ERalpha pathways . ^^^ Although ERalpha and ERbeta are expressed in many breast cancer cells , the response of ERbeta to ErbB 2 signaling is less well defined . ^^^ In the present study , we demonstrate that ERbeta activity can be modulated by ErbB 2 signaling in ER expressing breast cancer cells . ^^^ The estrogen dependent transcriptional activity of ERbeta was altered in a manner similar to ERalpha by either activation of ErbB2 / ErbB3 signaling by growth factor heregulin beta or expression of a constitutively active mutant of ErbB 2 . ^^^ However , as opposed to ERalpha , the p 38 MAPK pathway was found to be involved in liganded ERbeta repression activity by ErbB 2 signaling and in regulating estrogen responsive promoter occupancy by ERbeta . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In particular , the expression or activation of epidermal growth factor receptor and ERBB 2 are altered in many epithelial tumours , and clinical studies indicate that they have important roles in tumour aetiology and progression . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
At baseline , Western Blot analysis demonstrated expression of erbB 2 , erbB 3 and erbB 4 receptors and multiple NRG isoforms . ^^^ Following 1 and 8 weeks of PRT , no changes erbB 2 , erbB 4 or NRG expression were observed . ^^^ Thus , erbB 2 , erbB 3 , erbB 4 and multiple NRG isoforms are natively expressed in human skeletal muscle . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Furthermore , decreased heterodimerization of ErbB 2 and ErbB 3 led to a reorganization in ErbB function in transfected cells as heterodimerization between epidermal growth factor receptor ( EGFR ) and ErbB 3 increased , whereas ErbB 3 activation remained almost the same . ^^^ Importantly , elimination of ErbB 2 signaling resulted in an increase in EGFR expression and activation in transfected cells . ^^^ Reorganization of ErbB family and cell survival signaling after Knock down of ErbB 2 in colon cancer cells . ^^^ The role of the ErbB family in supporting the malignant phenotype was characterized by stable transfection of a single chain antibody ( ScFv5R ) against ErbB 2 containing a KDEL endoplasmic reticulum retention sequence into GEO human colon carcinoma cells . ^^^ The antibody traps ErbB 2 in the endoplasmic reticulum , thereby down regulating cell surface ErbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PATIENTS AND METHODS : EGFR , ERBB 2 , ERBB 3 and ERBB 4 were evaluated immunohistochemically in normal urothelium ( NU , 15 ) , primary non metastasized invasive TCC ( NMC , 19 ) and in primary invasive TCCs with corresponding metastases ( MC , 51 , both specimens ) . ^^^ RESULTS : All NU samples expressed ERBB 4 , none expressed ERBB 2 and two expressed EGFR ; all staining was uniform throughout all cell layers . ^^^ There was no difference between NMCs and MCs in ERBB 2 , ERBB 3 and ERBB 4 , but the NMCs expressed more EGFR than both NU and MC samples . ^^^ CONCLUSION : We hypothesise that : ( 1 ) ERBB 4 is important for differentiation in NU ; ( 2 ) ERBB 2 is up regulated with carcinogenesis in the urinary bladder but does not discriminate between bladder cancer with or without metastases ; ( 3 ) EGFR may be a marker of indolent disease . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Interleukin 6 ( IL 6 ) has been shown to regulate both growth and neuroendocrine ( NE ) differentiation in some types of human cancer cells , and erbB 2 may be a critical component of IL 6 signaling . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
These drug resistant cells demonstrate continued dependence on EGFR and ERBB 2 signaling for their viability and have not acquired secondary EGFR mutations . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Coexistence of copy number changes of different genes ( INK4A , erbB 1 , erbB 2 , CMYC , CCND 1 and ZNF 217 ) in urothelial tumors . ^^^ The aim of this study was to establish the frequency of combinatorial and separate copy number changes of INK4A ( 9p21 ) , erbB 1 ( 7p11 ) , erbB 2 ( 17q17 21 ) , CMYC ( 8q24 ) , CCND 1 ( 11q13 ) and ZNF 217 ( 20q13 ) in urothelial tumors ; a tissue microarray of 159 urothelial bladder tumors was analyzed by fluorescence in situ hybridization . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Neoplastic Schwann cells within these neoplasms variably express the erbB kinases mediating NRG 1 responses ( erbB 2 , erbB 3 and / or erbB 4 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In vivo identification of the interaction site of ErbB 2 extracellular domain with its autoinhibitor . ^^^ Direct interference with the transforming potential of ErbB 2 has become a subject of great interest . ^^^ Disruption of critical ErbB 2 ectodomain interactions may lead to novel therapeutic approaches for the treatment of various tumors . ^^^ The mimetics can bind to the ErbB receptor specifically and block inter receptor interactions , resulting in the growth inhibition of ErbB 2 overexpressing cells in vitro . ^^^ In this study , three dimensional structure of herstatin , an autoinhibitor of ErbB 2 and ErbB 2 ectodomain complex was constructed by computer aided molecular modeling . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In this context , the recently delineated interplay between COX 2 derived PG signaling and other growth regulatory pathways , such as EGFR , ErbB 2 , IL 6 / GP130 , HGF / Met , TGF beta / Smad , and iNOS is expected to provide important therapeutic implications . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Enrichment of tumor cells was performed using either pre coupled HEA and / or ErbB 2 microbeads or a mixture of three monoclonal antibodies against HEA , ErbB 2 and EGFR . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Examples of coexpression of epidermal growth factor receptor ( EGFr ) and erbB 2 were also found . ^^^ Of the 58 tumors , 10 ( 17 . 2 % ) coexpressed EGFr and erbB 2 ; this was associated with T 1 disease ( P = 0 . 03 ) . ^^^ CONCLUSIONS : Varied levels of expression of both EGFr and erbB 2 appear to exist in human bladder cancer . ^^^ The observations presented suggest a role for EGFr and erbB 2 in the development and progression of bladder cancer that should be explored further . . ^^^ Compared with other tumors , the T 1 samples exhibited the greatest mean levels of erbB 2 protein expression ( P = 0 . 0028 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The synthesis and biological activity of a series of novel 5 substituted 4 hydroxy 8 nitroquinazolines that may function as inhibitors of EGFR and / or ErbB 2 related oncogenic signaling are described . ^^^ Although the enzyme assay showed a weak inhibition effect against both EGFR and ErbB 2 tyrosine kinases , the cell based antitumor activity turned out promising . ^^^ Compounds having 5 anilino substituent exhibit high potency with 5 ( 4 methoxy ) anilino 4 hydroxy 8 nitroquinazoline ( 1h ) being the best dual EGFR / ErbB 2 inhibitors , which effectively inhibited the growth of both EGFR ( MDA MB 468 , IC ( 50 ) < 0 . 01microM ) and ErbB 2 ( SK BR 3 , IC ( 50 ) =13microM ) overexpressing human tumor cell lines in vitro . ^^^ This study was the first attempt to identify new structural types of dual EGFR / ErbB 2 related signaling inhibitors by incorporation of the anilino group at the 5 position of 4 hydroxy 8 nitroquinazolines ' core structure , providing promising new templates for further development of potent inhibitors targeting both EGFR and ErbB 2 tyrosine kinases . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
On plastic , mainly ErbB 1 and ErbB 2 are expressed . ^^^ Culture on matrigel resulted in 11 fold increase in mRNA levels for ErbB 1 and ErbB 2 , and a 221 fold and 85 fold increase in the mRNA levels for ErbB 3 and ErbB 4 , respectively . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Biological properties of a human compact anti ErbB 2 antibody . ^^^ ErbB 2 is a prognostic factor and target of therapy for many carcinomas . ^^^ In contrast with the other ErbB receptors , ErbB 2 lacks a soluble direct ligand , but it is the preferred co receptor for the ErbB family members , forming heterodimers with more potent and prolonged signalling activity than that of homodimers . ^^^ We recently produced a new anti ErbB 2 antibody , Erb hcAb , by fusion of Erbicin , a human , anti ErbB 2 scFv , selectively cytotoxic to ErbB 2 positive cells , and a human Fc domain . ^^^ Here , we describe the main properties of Erb hcAb , using as a reference Herceptin , an anti ErbB 2 humanized monoclonal currently employed in clinical immunotherapy . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Sections containing bronchi were evaluated for epithelial cell proliferation using immunohistochemistry for a nuclear proliferation antigen , Ki 67 , and image analysis ; immunohistochemistry for basal cells using a cytokeratin 5 / 14 antibody ; and immunohistochemistry for the epidermal growth factor receptor and ErbB 2 , two receptor tyrosine kinases implicated in epithelial proliferation and differentiation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We simultaneously analyzed the somatic mutations of EGFR , K RAS , PIK3CA and BRAF genes in the squamous cell carcinoma with the ERBB 2 mutation , and found that the tumor did not harbor any EGFR or ERBB 2 or K RAS or PIK3CA or BRAF gene mutation , either . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In many human lung adenocarcinoma cell lines , a pathway involving epidermal growth factor receptor ( EGFR ) , ErbB 2 and ErbB 3 receptors , phosphatidyl inositol 3 kinase ( PI3K ) , Akt , glycogen synthase kinase 3 beta ( GSK 3 beta ) , and cyclin D 1 controls cell growth , survival , and invasiveness . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Systematic copy number analysis of tyrosine kinase genes identified high level amplification of EGFR in three NSCLC specimens , FGFR 1 in two specimens and ERBB 2 and MET in one specimen each . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Previous studies have shown that constitutive activation of epidermal growth factor receptor ( EGFR ) and ErbB 2 by elevated autocrine transforming growth factor alpha ( TGF alpha ) expression plays an important role in colon cancer progression . ^^^ Coexpression of EGFR and ErbB 2 is found in a subset of colon cancers and may cooperatively promote cancer cell growth and survival , as heterodimerization is known to provide for diversification of signal transduction . ^^^ Finally , Western blot analysis showed significant inhibition of phosphorylation of both EGFR and ErbB 2 by the combination treatment . ^^^ These data suggest that the strategy to target both EGFR and ErbB 2 simultaneously might result in more efficient inhibition of tumor growth than to target single receptor alone . . ^^^ Synergy of epidermal growth factor receptor kinase inhibitor AG 1478 and ErbB 2 kinase inhibitor AG 879 in human colon carcinoma cells is associated with induction of apoptosis . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
EGFR and erbB 2 mutation status in Japanese lung cancer patients . ^^^ We have investigated EGFR and erbB 2 mutation status in 95 surgically treated nonsmall cell lung cancer ( NSCLC ) cases from Nagoya City University Hospital . ^^^ There was a significantly higher erbB 2 positive ( 2+ / 3+ ) ratio in EGFR mutant patients ( 13 / 25 , 52 . 0 % ) compared to EGFR wild type patients ( 10 / 62 , 16 . 1 % ; p = 0 . 0247 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Activation of ErbB 2 by overexpression or by transmembrane neuregulin results in differential signaling and sensitivity to herceptin . ^^^ Particular attention has focused on ErbB 2 , whose activation may occur by receptor overexpression or by ligand induced oligomerization with other ErbB receptors . ^^^ Whether these two modes of ErbB 2 activation cause the same biological responses is unknown . ^^^ Here , we uncovered important differences in the signaling , proliferation rates , and the response to anti ErbB 2 antibodies when comparing MCF 7 cells expressing the ligand neuregulin , to MCF 7 cells overexpressing ErbB 2 . ^^^ Expression of neuregulin caused higher proliferation than ErbB 2 overexpression . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Towards this end , we have investigated the effects of a representative Hsp 90 inhibitor , 17 ( dimethylaminoethylamino ) 17 demethoxygeldanamycin ( 17DMAG ) , on the radiosensitivity of a panel of human tumor cell lines . 17DMAG was previously shown to enhance the radiosensitivity of a number of human cell lines , which correlated with the loss of ErbB 2 . ^^^ We now report on cell lines in which 17DMAG induced the degradation of ErbB 2 , yet had no effect on radiosensitivity . ^^^ Whereas individual treatments with siRNA to ErbB 3 or 17DMAG had no effect on radiosensitivity , the combination , which reduced both ErbB 2 and ErbB 3 , resulted in a significant enhancement in AsPC 1 radiosensitivity . ^^^ However , for cell lines sensitized by 17DMAG , treatment with siRNA to ErbB 2 , which reduced ErbB 1 activity , had no effect on radiosensitivity . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In addition , we examined the effect of another quinazoline derivative , GW 2974 , which is able to block the activation of both the EGFR and erbB 2 , in this model . ^^^ The results also suggest that activation of the EGFR plays an important role in development of BTC in this model and that targeting both the EGFR and erbB 2 may be an effective strategy for treatment of this disease . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Combining lapatinib ( GW 572016 ) , a small molecule inhibitor of ErbB 1 and ErbB 2 tyrosine kinases , with therapeutic anti ErbB 2 antibodies enhances apoptosis of ErbB 2 overexpressing breast cancer cells . ^^^ Here , apoptosis of ErbB 2 overexpressing breast cancer cells was enhanced by combining lapatinib , an inhibitor of ErbB 1 and ErbB 2 tyrosine kinases , with anti ErbB 2 antibodies , including ( 1 ) trastuzumab , a humanized monoclonal antibody , and ( 2 ) pAb , rabbit polyclonal antisera generated by vaccination with a human ErbB 2 fusion protein . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Biochemical studies revealed that TKI 28 potently inhibited the activities of tyrosine kinases such as ErbB 2 , EGFR , KDR , PDGFRbeta , c kit and c Src , but had little effect on Flt 1 in cell free system . ^^^ Computer modeling of the pyrido pyrimidine class compound , TKI 28 ( 6 ( 2 , 6 dichlorophenyl ) 8 methyl 2 phenylamino 8H pyrido [ 2 , 3 d ] pyrimidine 7 one ) , predicted that the compound would dock well in the ATP pocket of the ErbB 2 tyrosine kinase , yielding a high binding affinity for ErbB receptors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Baseline erbB 3 and erbB 4 revealed the highest frequencies of expression , while erbB 2 was the lowest . ^^^ At 50 mg / d , CI 1033 had a more favorable adverse events profile than at 200 mg / d . erbB 3 and erbB 4 receptors showed the highest expression in tumor samples while erbB 2 revealed the least . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The therapeutic utility of trastuzumab ( ' Herceptin ' ) in breast cancer patients with tumours that overexpress erbB 2 established the principle that targeted inhibition of specific signal transduction pathways can provide a new approach to cancer treatment . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
EGFR activation can also result in transphosphorylation of tyrosine resides in the C terminal region of the related receptors ErbB 2 , ErbB 3 and ErbB 4 in heterodimers which are formed upon ligand stimulation . ^^^ Our results demonstrated that ( 1 ) EGFR kinase can efficiently phosphorylate a broad range of diverse peptide sequences representing ErbB sites ; ( 2 ) certain ErbB 2 , ErbB 3 and ErbB 4 sites had higher specificity constants than any EGFR sequence and ( 3 ) EGF stimulation consistently increases the k ( cat ) approx . 5 fold , but does not significantly alter the K ( m ) for any ErbB peptides . ^^^ EGFR activation can also result in transphosphorylation of tyrosine resides in the C terminal region of the related receptors ErbB 2 , ErbB 3 and ErbB 4 in heterodimers which are formed upon ligand stimulation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
T10c12 decreased the levels of ErbB 1 , ErbB 2 , and ErbB 3 proteins and transcripts in a dose dependent manner , whereas c9t11 had no effect . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We have recently shown that peptides corresponding to the transmembrane domains of the epidermal growth factor ( EGF ) and ErbB 2 receptors inhibit their corresponding receptor activation in cancer cell lines . ^^^ Peptides corresponding to the transmembrane domains of the EGF receptor and ErbB 2 are able to inhibit specifically the autophosphorylation of insulin receptors with the corresponding domain . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Concomitant expression of TGF alpha , EGFR , and ErbB 2 gives a strong proliferative drive in vitro and in vivo . ^^^ We aimed to determine whether TGF alpha , EGFR , and ErbB 2 are present in human synovial joints , especially during rheumatoid arthritis ( RA ) . ^^^ TGF alpha mRNA and TGF alpha , ErbB 2 , EGFR , and CD 68 immunoreactivity were detected in knee synovial biopsies ( 6 RA / 2 OA / 6 control ) using in situ hybridization and immunohistochemistry . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Studies using a 20 , 000 element ( 20K ) cDNA microarray demonstrate decreased transcript expression of ErbB 1 ( epidermal growth factor receptor ) and ErbB 2 in DU 145 ( prostate ) and ErbB 2 in SKBr 3 ( breast ) cancer cell lines . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Pharmacodynamic studies were performed by determining serum and tissue ERBB 2 and EGFR . ^^^ The comparison of pre and post therapy ERBB 2 and EGFR values was not statistically significant between the subgroups of patients regarding responsiveness to treatment . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We employed human GrB as an effector function in chimeric fusion proteins that also contain the EGFR ligand TGFalpha or an ErbB 2 specific single chain antibody fragment ( scFv ) for selective targeting to tumor cells . ^^^ GrB TGFalpha ( GrB T ) and GrB scFv ( FRP 5 ) ( GrB 5 ) molecules expressed in the yeast Pichia pastoris were bifunctional , cleaving synthetic and natural GrB substrates , and binding specifically to cells expressing EGFR or ErbB 2 target receptors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We also demonstrated that both PRL and leptin ( LEP ) are capable of transactivation of the oncogenic receptors erbB 2 and erbB 3 . ^^^ Upon PRL or LEP stimulation of HEK 293T cells transfected with LEP or PRL receptors and erbB 2 or erbB 3 , erbB proteins are first phosphorylated and then activate MAPK ( erk1 / erk2 ) . ^^^ However , the FRET experiments failed to document any evidence of a direct interaction between erbB 2 and the PRL or LEP receptors , suggesting that erbB activation probably occurs via activated JAK 2 , translocated from the respective receptors to erbB2 . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
BACKGROUND : ErbB 2 ( HER 2 ) , a member of the epidermal growth factor ( EGF ) receptor family , is a class 1 transmembrane receptor tyrosine kinase . ^^^ Although erbB 2 has no known physiologic ligand , it can form complexes with other members of the family and undergo transactivation of its very potent kinase activity , thereby initiating downstream signaling and cell proliferation . ^^^ ErbB 2 is a frequent pathologic marker in ductal invasive breast carcinomas and is targeted by using a specific humanized monoclonal antibody , trastuzumab ( Herceptin ) . ^^^ The antibody is effective in only 20 % to 50 % of erbB 2 positive tumors , and this resistance , as yet poorly understood , constitutes a major therapeutic challenge . ^^^ We used EGF and trastuzumab covered paramagnetic microspheres , quantitative confocal laser scanning microscopy , and digital image processing to investigate the ( trans ) activation of and local signal propagation from erbB 1 and erbB 2 on trastuzumab sensitive and resistant carcinoma cell lines expressing these receptors at high levels . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The c Src tyrosine kinase associates with the catalytic domain of ErbB 2 : implications for ErbB 2 mediated signaling and transformation . c Src associates with and is activated by the ErbB 2 receptor tyrosine kinase , but is unable to bind the EGFR . ^^^ Significantly , EGFR could be converted into a receptor capable of binding c Src by replacement of a catalytic domain of ErbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Zinc finger transcription factors designed for bispecific coregulation of ErbB 2 and ErbB 3 receptors : insights into ErbB receptor biology . ^^^ In this work , we altered the levels of ErbB 2 and ErbB 3 receptors , individually and in combination , by using 6 finger and 12 finger synthetic zinc finger protein artificial transcription factors ( ATFs ) in an epidermoid squamous cell carcinoma line , A 431 . ^^^ We successfully designed 12 finger ATFs capable of coregulating ErbB 3 and ICAM 1 or ErbB 2 and ErbB 3 . ^^^ With ATFs , the effects of changes in ErbB 2 and ErbB 3 receptor levels were evaluated by using cell proliferation , cell migration , and cell signaling assays . ^^^ Cell proliferation was increased when ErbB 2 and ErbB 3 were both overexpressed . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The human ErbB family of receptor tyrosine kinases comprises the epidermal growth factor receptor ( EGFR / ErbB1 / HER1 ) , ErbB 2 ( HER2 / Neu ) , ErbB 3 ( HER 3 ) , and ErbB 4 ( HER 4 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
By constructing stably transfected cells harboring the same amount of epidermal growth factor ( EGF ) receptor ( EGFR ) , but with increasing overexpression of ErbB 2 , we have demonstrated that ErbB 2 efficiently inhibits internalization of ligand bound EGFR . ^^^ Apparently , ErbB 2 inhibits internalization of EGF bound EGFR by constitutively driving EGFR ErbB 2 hetero / oligomerization . ^^^ We have demonstrated that ErbB 2 does not inhibit phosphorylation or ubiquitination of the EGFR . ^^^ Our data further indicate that the endocytosis deficiency of ErbB 2 and of EGFR ErbB 2 heterodimers / oligomers can not be explained by anchoring of ErbB 2 to PDZ containing proteins such as Erbin . ^^^ Instead , we demonstrate that in contrast to EGFR homodimers , which are capable of inducing new clathrin coated pits in serum starved cells upon incubation with EGF , clathrin coated pits are not induced upon activation of EGFR ErbB 2 heterodimers / oligomers . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
To evaluate the prognostic impact of the ErbB receptors expression profile , we analyzed a well characterized series of 145 primary breast carcinomas for the simultaneous expression of epidermal growth factor receptor ( EGFR / HER 1 ) , ErbB 2 ( HER 2 ) , ErbB 3 ( HER 3 ) , and ErbB 4 ( HER 4 ) , using immunohistochemistry . ^^^ Expression of EGFR , ErbB 2 , ErbB 3 , and ErbB 4 was observed in 31 ( 21 . 4 % ) , 65 ( 44 . 8 % ) , 72 ( 49 . 7 % ) , and 81 ( 55 . 9 % ) of the cases , respectively . ^^^ As expected , ErbB 2 expression was associated with reduced overall survival at 15 years of follow up ( P = 0 . 04 ) , even after adjusting for a series of other prognostic factors ( P = 0 . 05 ) . ^^^ Moreover , cumulative analysis of ErbB 2 / 3 / 4 expression showed a strong positive association between higher total ErbB 2 / 3 / 4 expression score and worse prognosis ( P = 0 . 002 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
FAK signaling is critical for ErbB 2 / ErbB 3 receptor cooperation for oncogenic transformation and invasion . ^^^ We demonstrate that focal adhesion kinase ( FAK ) is essential for oncogenic transformation and cell invasion that is induced by ErbB 2 and 3 receptor signaling . ^^^ ErbB 2 / 3 overexpression in FAK deficient cells fails to promote cell transformation and rescue chemotaxis deficiency . ^^^ Restoration of FAK rescues both oncogenic transformation and invasion that is induced by ErbB 2 / 3 in vitro and in vivo . ^^^ The activation of ErbB 2 / 3 regulates FAK phosphorylation at Tyr 397 , 861 , and 925 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Using two pancreatic cancer cell lines that express different EGFR and ErbB 2 levels , we analyzed the activity of Iressa and evaluated its modulation effect on four conventional cytotoxic drugs : gemcitabine , oxaliplatin , docetaxel and SN 38 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Response of some head and neck cancers to epidermal growth factor receptor tyrosine kinase inhibitors may be linked to mutation of ERBB 2 rather than EGFR . ^^^ The objective of this study was to determine if such mutations , or recently reported mutations in ERBB 2 , also underlie EGFR TKI responsiveness in SCCHN patients . ^^^ EXPERIMENTAL DESIGN : We sequenced the kinase domain of EGFR and exon 20 of ERBB 2 in tumor specimens from eight responsive patients . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The ErbB 1 and ErbB 2 receptors are oncogenes with therapeutic significance in human cancer , whereas the transforming potential of the related ErbB 4 receptor has remained controversial . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : To examine the relationship of epidermal growth factor receptor ( EGFR ) expression to ErbB 2 signaling activity in breast cancer and the impact that this interaction has on the prognosis of patients with early stage breast cancer . ^^^ Immunohistochemical assays for ErbB 2 , phosphorylated ( activated ) ErbB 2 , and EGFR were performed , and the results were correlated with clinicopathologic variables and outcome . ^^^ RESULTS : EGFR expression was detectable in 15 % of 807 invasive breast cancers , including 35 % of the 306 ErbB 2 positive patients . ^^^ Conversely , the majority ( 87 % ) of EGFR positive tumors co overexpressed ErbB 2 . ^^^ Ninety seven percent of tumors with phosphorylated ErbB 2 co overexpressed EGFR . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Gain of function analyses show that EGFR , ErbB 2 , and ErbB 4 induce ectopic tumor like cell mass that contains increased numbers of mitotic cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Most notably , EGFR and ErbB 2 become markedly more promiscuous as the threshold is lowered , whereas ErbB 3 does not . ^^^ Because EGFR and ErbB 2 are overexpressed in many human cancers , our results suggest that the extent to which promiscuity changes with protein concentration may contribute to the oncogenic potential of receptor tyrosine kinases , and perhaps other signalling proteins as well . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Proliferation of erbB 2 overexpressing BT 474 cells was inhibited to a greater extent than proliferation of EGFR overexpressing A 431 cells following exposure to SUCI 02 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Therefore , we assessed the immunoreactivity for EGFR ( ErbB 1 ) , ErbB 2 , and ErbB 3 in nerve biopsies from patients with different forms of Charcot Marie Tooth disease , type 1 , ( CMT 1 ) , as compared to others with inflammatory neuropathies and controls . ^^^ Overexpression of ErbB 2 and ErbB 3 receptors in Schwann cells of patients with Charcot Marie tooth disease type 1A . ^^^ The most notable changes consisted in the overexpression of ErbB 2 and ErbB 3 by SCs of nerves from CMT1A patients . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ERBB 2 is a member of the epidermal growth factor receptor ( EGFR ) family . ^^^ We simultaneously analyzed the somatic mutations of EGFR , K RAS , PIK3CA and BRAF genes in the sample with the ERBB 2 mutation , and found that this metastatic carcinoma did not harbor any of the mutations . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The EGFR is a member of the ErbB receptor tyrosine kinase ( TK ) family , which also includes ErbB 2 ( HER2 / neu ) , ErbB 3 ( HER 3 ) , and ErbB 4 ( HER 4 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
A new generation of small molecule TKIs is emerging in which multiple receptor pathways , including ErbB 2 and vascular endothelial growth factor receptor , can be simultaneously targeted with EGFR . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Among ErbB tyrosine kinase receptors , EGF receptor ( EGFR ) and ErbB 2 were selectively activated by tRA treatment in skin from wild type mice , while the activation of these ErbB receptors was significantly reduced in the skin of HB EGF null mice . ^^^ These results indicate that expression of HB EGF and generation of its soluble form , followed by activation of EGFR and ErbB 2 , are pivotal processes in tRA induced epidermal hyperplasia . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Frequency and clinicopathologic correlates of ErbB 1 , ErbB 2 , and ErbB 3 immunoreactivity in urothelial tumors of upper urinary tract . ^^^ OBJECTIVES : To investigate the frequency and clinicopathologic correlates of ErbB 1 , ErbB 2 , and ErbB 3 receptor expression in patients with upper urothelial carcinoma . ^^^ METHODS : Immunohistochemical staining for ErbB 1 , ErbB 2 , and ErbB 3 was done with serial sections from archival specimens of 94 patients who underwent nephroureterectomy plus bladder cuff resection for urothelial carcinoma of the renal pelvis and ureter ( median follow up 40 months , range 1 to 177 ) . ^^^ RESULTS : ErbB 1 , ErbB 2 , and ErbB 3 expression was present in 9 ( 9 . 5 % ) , 13 ( 13 . 8 % ) , and 26 ( 27 . 7 % ) tumors , respectively . ^^^ ErbB 2 expression was significantly associated with tumor invasiveness ( P = 0 . 03 ) , and ErbB 1 and ErbB 3 expression was not . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
However , in all three cell lines , 17AAG increased radiation induced apoptosis by reducing the expression of EGFR and ErbB 2 and inhibiting the phosphorylation of Akt . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In human breast cancer , estrogen receptor alpha ( ERalpha ) , progesterone receptor ( PR ) and human epidermal growth factor receptor ( ERBB 2 ) status are currently determined using different techniques . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Braf , EGFR , and erbB 2 mutations also were analyzed by reverse transcript polymerase chain reaction ( RT PCR ) and direct sequencing . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunoblot analysis showed that neither genistein nor daidzein decreased the protein levels of either of the epidermal growth factor receptors , ErbB 2 or ErbB 3 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We simultaneously analyzed the somatic mutations of EGFR , K RAS , PIK3CA , and BRAF genes in the 16 samples with ERBB 2 mutations , and found that all of the 3 colorectal carcinoma samples with ERBB 2 mutations harbored K RAS mutations . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Blockade of EGFR and ErbB 2 by the novel dual EGFR and ErbB 2 tyrosine kinase inhibitor GW 572016 sensitizes human colon carcinoma GEO cells to apoptosis . ^^^ Recently , efforts have been made to develop novel 4 anilinoquinazoline and pyridopyrimidine derivatives to inhibit EGFR and ErbB 2 kinases simultaneously . ^^^ In this study , we tested the efficacy of a novel reversible dual inhibitor GW 572016 compared with the selective EGFR and ErbB 2 tyrosine kinase inhibitors ( TKI ) AG 1478 and AG 879 and their combination , using the human colon adenocarcinoma GEO mode . ^^^ Western blot analysis revealed that AG 1478 and AG 879 were unable to suppress both EGFR and ErbB 2 activation as well as the downstream mitogen activated protein kinase ( MAPK ) and AKT pathways as single agents . ^^^ In contrast , GW 572016 suppressed the activation of EGFR , ErbB 2 , MAPK , and AKT in a concentration dependent manner . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
For this purpose , we successfully assayed trastuzumab , a monoclonal antibody against ErbB 2 , and gefitinib , an epidermal growth factor receptor tyrosine kinase receptor inhibitor . ^^^ Target based agents against ErbB 2 , epidermal growth factor receptor , or both such as trastuzumab or gefitinib might increase the efficiency of purging . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NEU ( ERBB 2 ) and other members of the epidermal growth factor receptor ( EGFR ) family have been implicated in human prostate cancer ( CAP ) development and progression to an androgen independent state , but the extent of involvement and precise role of this signaling pathway remain unclear . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The aim of this study was to investigate the relationships between quantitative levels of pY 1248 ERBB2 ( p ERBB 2 ) and the expression of epidermal growth factor receptor ( EGFR ) family members , and whether p ERBB 2 could provide additional prognostic value compared with established prognostic markers . ^^^ Phosphorylated ERBB 2 correlated with EGFR and ERBB 2 , and inversely with oestrogen receptor ( ER ) , progesterone receptor ( PgR ) and ERBB 4 expression levels . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Negatively correlated genes clustered into two main groups with distinct expression profiles and drug correlations , represented by EGFR and ERBB 2 ( Her 2 / Neu ) . ^^^ Accordingly , no synergism was observed between EGFR and ERBB 2 inhibitors . ^^^ However , combinations with classical anticacer drugs were not correlated with EGFR and ERBB 2 expression in four cell lines tested , suggesting complex interactions in combination treatments . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Using specific ErbB receptor inhibitors and depletion of receptors by RNA interference ( RNAi ) , we established that , surprisingly , activation of Rac by HRG is mediated not only by ErbB 3 and ErbB 2 but also by transactivation of EGFR , and it is independent of ErbB 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We have previously shown that VSs produce the glial growth factor , neuregulin 1 ( NRG 1 ) , and its receptors , ErbB 2 and ErbB 3 . ^^^ We confirm that human VSs , which express markers of immature and denervated SCs , also express endogenous NRG 1 and activated ErbB 2 . ^^^ We find that a blocking anti NRG 1 antibody and trastuzumab ( Herceptin , HCN ) , a humanized anti ErbB 2 inhibitory monoclonal antibody , effectively inhibit NRG 1 induced SC proliferation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Tissue microarray analysis of EGFR and erbB 2 copy number changes in ovarian tumors . ^^^ The objective of this study was to assess the implication of copy number changes of epidermal growth factor receptor ( EGFR ) and erbB 2 genes in the etiology and progression of ovarian tumors . ^^^ No amplification of EGFR and erbB 2 genes was established in tumors with low malignant potency and in benign tumors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Grg 1 and Grg 5 both diminish p 53 protein levels ; however , only Grg 1 overexpression induces elevated levels of ErbB 1 and ErbB 2 receptor tyrosine kinases . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Antiestrogen resistant breast cancer often shows increased expression of the epidermal growth factor receptor ( EGFR ) family members , EGFR and ErbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Neoplastic Schwann cells almost uniformly express erbB 2 and erbB 3 , 2 membrane receptor tyrosine kinases mediating NRG 1 and NRG 2 action . ^^^ ErbB 2 , the preferred dimerization partner for all erbB kinases , is constitutively phosphorylated in schwannomas . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
To further determine the genetic and molecular characteristics of tumors carrying EGFR gene mutations , we investigated the EGFR gene status in lung adenocarcinomas and evaluated its association with specific characteristics of the patients and tumors , such as mutations at KRAS and p 53 , EGFR and ErbB 2 gene amplification , levels of EGFR and HER 2 proteins , and levels of downstream effectors of EGFR , such as phospho extracellular signal regulated kinase and phospho S 6 proteins . ^^^ A tissue microarray containing 37 lung tumors was constructed to determine , by fluorescence in situ hybridization analysis , the number of copies of EGFR and ErbB 2 genes and , by immunohistochemistry , the levels of EGFR , HER 2 , phospho ERK , and phospho S 6 proteins . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : Monoclonal antibodies , such as herceptin and trastuzumab , against the epidermal growth factor receptor ErbB 2 ( also known as HER2 / neu ) are an effective therapy for breast cancer patients with overexpression of ErbB 2 . ^^^ Herceptin sensitizes ErbB 2 overexpressing cells to apoptosis by reducing antiapoptotic Mcl 1 expression . ^^^ RESULTS : This treatment resulted in reduced expression of ErbB 2 and the antiapoptotic Bcl 2 family member Mcl 1 in MDA MB 231 cells . ^^^ In 29 human breast tumors immunostained for ErbB 2 and Mcl 1 , we found that when ErbB 2 was overexpressed , there was a corresponding increase in Mcl 1 expression . ^^^ DISCUSSION : Using murine fibroblasts that express human ErbB 2 , but no other ErbB family member ( NE 2 ) , these cells showed resistance to both taxol and etoposide induced apoptosis compared with parental cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Six genes were over expressed ( ERBB 2 , TGFA , HB EGF , AREG , EREG and EPGN ) , 3 were under expressed ( ERBB 1 , ERBB 4 and NRG 4 ) and 2 were over or under expressed ( ERBB 3 and BTC ) . ^^^ ERBB 2 and AREG expression differed between early stage tumors ( pTa grade 1 ) and normal samples . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Expression of ErbB 4 receptor is correlated with the incidence of non metastatic types of human cancers , whereas the overexpression of other ErbB receptor families ( ErbB1 / EGFR , ErbB 2 and ErbB 3 ) is correlated to the formation of metastatic tumors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Structure activity relationships for inhibition of erbB 1 , erbB 2 , and erbB 4 were determined for a series of alkynamide analogues of quinazoline and pyrido [ 3 , 4 d ] pyrimidine based compounds . ^^^ The compounds showed pan erbB enzyme inhibition but were on average about 10 fold more potent against erbB 1 than against erbB 2 and erbB 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 1 and erbB 4 do not compensate for the loss of erbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Differentiation of human airway epithelia is dependent on erbB 2 . ^^^ A clinical case documented a reversible change in airway epithelial differentiation that coincided with the initiation and discontinuation of trastuzumab , an anti erbB 2 antibody . ^^^ This prompted the investigation into whether blocking the erbB 2 receptor alters differentiation of the airway epithelium . ^^^ These data show that erbB 2 stimulation is required for maintaining epithelial differentiation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
HB EGF signaling through ErbB 2 is essential for the maintenance of homeostasis in the adult heart , whereas HB EGF signaling through EGFR is required during cardiac valve development . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The inappropriate activation of one or more members of the ErbB family of receptor tyrosine kinases [ ErbB 1 ( EGFR ) , ErbB 2 , ErbB 3 , ErbB 4 ] has been linked with oncogenesis . ^^^ ErbB 2 is frequently coexpressed with ErbB 3 in breast cancer cells and in the presence of the ligand heregulin ( HRG ) the ErbB 2 / ErbB 3 receptors form a signaling heterodimer that can affect cell proliferation and apoptosis . ^^^ The major goal of the present study was to determine whether endogenous HRG causes autocrine / paracrine activation of ErbB 2 / ErbB 3 and contributes to the proliferation of mammary epithelial tumor cells . ^^^ Tyrosine phosphorylated ( activated ) ErbB 2 and ErbB 3 receptors were detected in the majority of extracts from tumors that had formed spontaneously or as a result of oncogene expression . ^^^ Various mouse mammary cell lines also contained activated ErbB 2 / ErbB 3 and HRG transcripts . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Analysis of tumor derived endothelial cells showed that they express EGFR , ErbB 2 , and ErbB 4 , whereas their normal counterparts express ErbB 2 , ErbB 3 , and ErbB 4 . ^^^ As a consequence of their expressing EGFR , tumor endothelial cells responded to EGF and other EGF family members by activating both EGFR and ErbB 2 , by activating the downstream mitogen activated protein kinase pathway , and by enhanced proliferation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
RESULTS : On a univariate basis , the following features were significantly associated with worse survival : high pathologic tumor or nodal class , histologic grade , epidermal growth factor receptor , ERBB 2 , MYC , or TP 53 ; absent estrogen receptor ( ER ) or progesterone receptor ; and low BCL 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 2 , a binding partner of epidermal growth factor receptor ( EGFR ) , and EGFR modulated Ras activity , and integrin alpha ( 6 ) beta ( 4 ) regulated phospho EGFR level without affecting EGFR expression . ^^^ In summary , we propose a novel mechanism for ErbB 2 up regulation and Ras activation in serum depleted breast cancer cells ; integrin alpha ( 6 ) beta ( 4 ) regulates the expression of ErbB 2 and the subsequent phosphorylation of EGFR and activation of Ras . ^^^ A novel mechanism for integrin mediated ras activation in breast carcinoma cells : the alpha6beta4 integrin regulates ErbB 2 translation and transactivates epidermal growth factor receptor / ErbB2 signaling . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Activation of ErbB 2 by 2 methyl 1 , 4 naphthoquinone ( menadione ) in human keratinocytes : role of EGFR and protein tyrosine phosphatases . ^^^ We here demonstrate that ErbB 2 is activated via the epidermal growth factor receptor ( EGFR ) upon exposure of cultured human keratinocytes to 2 methyl 1 , 4 naphthoquinone ( menadione ) . ^^^ Both ErbB 2 and EGFR are shown to be regulated by protein tyrosine phosphatases that are inhibited by menadione , giving rise to the hypothesis that phosphatase inhibition by menadione may result in a net activation of EGFR and an enhanced ErbB 2 phosphorylation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ErbB 1 is followed by ErbB 3 , ErbB 2 and ErbB 4 in MCF 7 at both the protein and mRNA levels . ^^^ In MDA MB 231 cells , ErbB 1 is followed by ErbB 2 , ErbB 4 and ErbB 3 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
After 3 days of permanent application , TGFalpha induced a major downregulation of both erbB 1 and erbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In addition , analysis of membrane fractions obtained using a linear sucrose gradient showed that ErbB 2 , epidermal growth factor receptor ( EGFR ) and Shc p 66 ( proteins correlated with the ErbB 2 signal transduction pathway ) were preferentially enriched in lipid rafts together with gangliosides . ^^^ Blocking of endogenous ganglioside synthesis by ( + / ) threo 1 phenyl 2 decanoylamino 3 morpholino 1 propanol hydrochloride ( [ D ] PDMP ) induced a drastic cell surface redistribution of ErbB 2 , EGFR and Shc p 66 , within the Triton soluble fractions , as revealed by linear sucrose gradient analysis . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Muc 4 ErbB 2 complex formation and signaling in polarized CACO 2 epithelial cells indicate that Muc 4 acts as an unorthodox ligand for ErbB 2 . ^^^ Muc 4 serves as an intramembrane ligand for the receptor tyrosine kinase ErbB 2 . ^^^ The time to complex formation and the stoichiometry of the complex were determined to be < 15 min and 1 : 1 by analyses of Muc 4 and ErbB 2 coexpressed in insect cells and A 375 tumor cells . ^^^ In polarized CACO 2 cells , Muc 4 expression causes relocalization of ErbB 2 , but not its heterodimerization partner ErbB 3 , to the apical cell surface , effectively segregating the two receptors . ^^^ The apically located ErbB 2 is phosphorylated on tyrosines 1139 and 1248 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Whereas the epidermal growth factor receptor , ErbB 2 and ErbB 3 are positively associated with various cancers , clinical studies of ErbB 4 in breast cancer are contradictory . ^^^ Results from tissue culture analyses and some clinical studies suggested that ErbB 4 is either a tumor suppressor or is a negative regulator of ErbB 2 driven tumors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : The ErbB 1 and ErbB 2 receptors have been implicated in prostate cancer progression , but less is known about the role and biology of other ErbB receptor family members in prostate cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Here we establish a model of acquired resistance to N { 3 chloro 4 [ ( 3 fluorobenzyl ) oxy ] phenyl } 6 [ 5 ( { [ 2 ( methylsulfonyl ) ethyl ] amino } methyl ) 2 furyl ] 4 quinazolinamine ( lapatinib ) , an inhibitor of ErbB 2 and ErbB 1 tyrosine kinases by chronically exposing lapatinib sensitive ErbB 2 overexpressing breast cancer cells to lapatinib , simulating the clinic where lapatinib is administered on a daily chronic basis . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Controlled activation of ErbB1 / ErbB2 heterodimers promote invasion of three dimensional organized epithelia in an ErbB 1 dependent manner : implications for progression of ErbB 2 overexpressing tumors . ^^^ Using such a method , we show that whereas both ErbB 2 homodimers and ErbB 1 ErbB2 heterodimers were equally potent in activating the Ras / mitogen activated protein kinase pathway , the heterodimers were more potent in activating the phosphoinositide 3 ' kinase ( PI3K ) and phospholipase Cgamma 1 pathways than ErbB 2 homodimers . ^^^ We combined the dimerization system with a three dimensional cell culture approach to show that whereas both ErbB 2 homodimers and ErbB 1 ErbB2 heterodimers induced disruption of three dimensional acini like structures , only heterodimers promoted invasion of cells through extracellular matrix . ^^^ Thus , we have identified cell invasion as a heterodimer specific biological outcome and suggest that coexpression of ErbB 1 may critically regulate invasive progression of ErbB 2 positive breast cancers . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The focus of this review will be on the generation of highly effective signaling inhibitors targeting members of the erbB family of receptor tyrosine kinases , EGFR and ErbB 2 , also known as transmembrane Type 1 receptor tyrosine kinases of the HER family of receptors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The depletion of ErbB family receptors , including epidermal growth factor receptor ( EGFR ) , ErbB 2 , and ErbB 3 , was also observed . 5GG treatment also led to a dose dependent decrease in the expression of the estrogen activated cyclin D 1 expression . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Expression and genomic status of EGFR and ErbB 2 in alveolar and embryonal rhabdomyosarcoma . ^^^ Both epidermal growth factor receptor ( EGFR ) and ErbB 2 play an important role in cancer biology and constitute promising molecular targets of therapy . ^^^ EGFR and ErbB 2 expression has been observed in rhabdomyosarcoma cell lines but not analyzed systematically in rhabdomyosarcoma tumors . ^^^ Tissue microarray sections representing 66 rhabdomyosarcoma tumors ( 34 embryonal rhabdomyosarcoma , 32 alveolar rhabdomyosarcoma ) were surveyed by immunohistochemistry using antibodies specific for EGFR and ErbB 2 . ^^^ EGFR and ErbB 2 expression was considered positive if the product of intensity and percentage was greater than 10 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The HSP 90 inhibitor 17 allylamino 17 demethoxygeldanamycin ( 17 AAG ) depletes some proteins involved in PI3K / AKT signaling , e . g . , ERBB 2 , epidermal growth factor receptor ( EGFR ) , and phosphorylated AKT ( p AKT ) . 17 AAG and paclitaxel were combined ( at a fixed 1 : 1 ratio of their IC ( 50 ) ) in four ovarian cancer cell lines that differ in expression of p AKT , EGFR , and ERBB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In hyperproliferative ACF , 44 % possessed significant increases in four EGFR signaling components : EGFR ( 9 . 5 + / 1 . 3 fold ) , phosphoactive ErbB 2 ( 2 . 6 + / 0 . 4 fold ) , phosphoactive extracellular signal regulated kinase ( 3 . 7 + / 1 . 1 fold ) , and cyclin D 1 ( 3 . 4 + / 0 . 8 fold ; P < 0 . 05 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
METHODS AND MATERIALS : Breast carcinoma cell lines with different ErbB RTK expression profiles were transduced with EGFR or ErbB 2 deletion mutants ( EGFR CD 533 and ErbB 2 CD572 ) using an adenoviral vector . ^^^ CONCLUSION : Expression of EGFR CD 533 inhibits the ErbB RTK network and radiosensitizes carcinoma cells irrespective of the ErbB RTK expression patterns , and ErbB 2 CD572 does not radiosensitize cells with low EGFR expression . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
According to the `` combi targeting ' ' concept , the EGFR tyrosine kinase ( TK ) inhibitory potency of compounds termed `` combi molecules ' ' is critical for selective growth inhibition of tumor cells with disordered expression of EGFR or its closest family member erbB 2 . ^^^ Selective antiproliferative studies in a pair of mouse fibroblast NIH3T3 cells , one of which NIH3T3 / neu being transfected with the erbB 2 oncogene , showed that IC ( 50 ) values for inhibition of EGFR TK could be good predictors of their selective potency against the serum stimulated growth of the erbB 2 tranfected cell line ( Pearson r = 0 . 8 ) . ^^^ On the basis of stability ( t ( 1 / 2 ) ) , EGFR TK inhibitory potency ( IC ( 50 ) ) , and selective erbB 2 targeting , compound 23 , a stable nitrosourea , was considered to have the structural requirements for further development . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Neuregulin activates erbB 2 dependent src / FAK signaling and cytoskeletal remodeling in isolated adult rat cardiac myocytes . ^^^ Cardiac myocyte erbB 2 expression is required for maintenance of normal cardiac structure and function , though its role in cardiac cellular physiology is incompletely understood . ^^^ We tested the hypothesis that erbB 2 signaling modulates focal adhesion formation via activation of a src / FAK pathway using adult rat ventricular myocytes in primary culture . ^^^ Using antibody and pharmacological inhibitor strategies , we found that FAK activation was erbB 2 and Src dependent , but independent of PI 3 kinase / Akt pathway . ^^^ Furthermore , NRG 1Beta stimulated the formation of a multiprotein complex between erbB 2 , FAK , p 130 ( CAS ) and paxillin within 30 min , and induced lamellipodia with longitudinal elongation of the myocytes within days . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
EGF promoted EGFr and ErbB 2 coassociation , stimulating tyrosine phosphorylation of both proteins . ^^^ A selective tyrphostin inhibitor of ErbB 2 suppressed EGF stimulated DNA synthesis , but maximum suppression required the blockade of the EGFr kinase as well . ^^^ Maximal EGF stimulation of DNA synthesis in vitro depends on the induction of ErbB 2 and involves an EGFr ErbB 2 heterodimer . ^^^ The emergence of ErbB 2 expression in cultured rat hepatocytes correlates with enhanced and diversified EGF mediated signaling . ^^^ Although ErbB 2 was not present in freshly isolated hepatocytes , EGF and insulin independently induced ErbB 2 while suppressing ErbB 3 expression . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
MUC 4 , a large molecular weight membrane bound glycoprotein , has recently been identified as a potential ligand for the ErbB 2 receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
This ALISA has been shown to be specific for epidermal growth factor receptor ( EGFR ) and the isoforms of EGFR encoded by alternate transcripts ( i . e . , sEGFRs ) ; it , therefore , does not detect other EGFR / ErbB receptor family members , i . e . , ErbB 2 , ErbB 3 , or ErbB 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
OBJECTIVE : Assess the amplification of CCND 1 , EMS 1 , PIK3CA , ERBB 1 , and ERBB 2 oncogenes in ethmoid sinus adenocarcinomas . ^^^ A semiquantitative evaluation of CCND 1 , EMS 1 , PIK3CA , ERBB 1 , and ERBB 2 amplification was performed by multiplex polymerase chain reaction . ^^^ ERBB 1 was amplified in 1 case ( 8 % ) , whereas none presented ERBB 2 amplification . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
It also raises interesting questions about the evolution of ErbB 2 and ErbB 3 : Does ErbB 2 in teleosts function differently from ErbB 2 in tetrapods in terms of ligand binding and intramolecular tethering . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The HER 2 protooncogene encodes a 185 kD transmembrane phosphoglycoproteins , human epidermal growth factor receptor 2 ( p185HER2 ) , whose amplified expression on the cell surface can lead to malignant transformation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Transformation mediated by the human HER 2 gene independent of the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
HER 2 is the human homolog of the rat proto oncogene neu and is closely related to the gene encoding the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Here , we show that cells harboring the G776insV _ G / C mutation in the related ERBB 2 tyrosine kinase ( also known as HER 2 or Neu ) , present in a small percentage of NSCLCs , are sensitive to HKI 272 , an irreversible dual specific kinase inhibitor targeting both EGFR and ERBB 2 . ^^^ Furthermore , HKI 272 abrogated autophosphorylation of both ERBB 2 and EGFR . ^^^ Non small cell lung cancer and Ba / F3 transformed cells harboring the ERBB 2 G776insV _ G / C mutation are sensitive to the dual specific epidermal growth factor receptor and ERBB 2 inhibitor HKI 272 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
This manifests itself for both ERBB 2 and ERBB 3 but is more pronounced and coupled directly to degradation for ERBB 3 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The erbB 2 copy number was not significantly correlated with the EGFR mutation or EGFR copy number in 59 cases . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Oncogenes ( H ras , erbB 2 , EGFR , MDM 2 , C MYC , CCND 1 ) , tumor suppressor genes ( p 53 , Rb , p 21 , p27 / KIP1 , p 16 , PTEN , STK 15 , FHIT , FEZ1 / LZTS1 , bc 10 ) , telomerase , and methylation have all been studied in bladder cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Model results applied to experimental data on ErbB 1 , ErbB 2 and ErbB 3 phosphorylation in H 292 human lung carcinoma cells support a hypothesis that key dephosphorylation activity for these receptors occurs largely in an intracellular , endosomal compartment rather than at the cell surface plasma membrane . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
EGFR is involved in the density dependent inhibition of cell growth , while coexpression of EGFR with erbB 2 can render normal cells transformed . ^^^ In this study , we have examined the effect of a species of p 185 that contains the transmembrane domain and the extracellular domain of p 185 ( c neu ) , on growth properties of a human malignant mesothelioma cell line that coexpresses EGFR and erbB 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
To go further in the characterization of the EGF pathway , we screened EGFR , ERBB 2 , ERBB 3 , KRAS , BRAF , and PIK3CA for mutations in 2 groups of White patients with nonsmall cell lung cancer ( 45 cancers from women and 46 cancers from men ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Protein tyrosine kinases such as HER 2 / c erbB 2 and the epidermal growth factor receptor ( EGFR ) have been linked specifically to breast cancer , and perturbations of HER 2 affect response to chemotherapy . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The EGF receptor ( EGFR ) and HER 2 are members of a growth factor receptor family . ^^^ EGFR : HER 2 or HER 4 : HER 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Within minutes of phorbol 12 myristate 13 acetate treatment , epidermal growth factor receptor and HER 2 tyrosine phosphorylation was decreased , while platelet derived growth factor receptor and insulin receptor autophosphorylation was upregulated . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
HER 2 , the erbB 2 / neu proto oncogene product , is a 185 kDa transmembrane glycoprotein related to the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The HER 2 gene encodes a cell surface glycoprotein with extensive homology to the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
A recently described oncogene that has an important association with aggressive human breast carcinoma is `` HER 2 , ' ' for human epidermal growth factor receptor 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The HER 2 promoter is different from the promoter of the epidermal growth factor receptor gene ( HER 1 ) , and the GC boxes which are typical of the promoter of the epidermal growth factor receptor gene are absent from the HER 2 promoter . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Using northern blot analysis and immunohistochemistry , we assessed the expression and distribution of human epidermal growth factor receptor 1 ( HER 1 ) , HER 2 , and HER 3 in pancreatic tissues obtained from patients with acute pancreatitis ( AP ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We find that these compounds are potent blockers of EGFR kinase and its homolog HER 2 kinase . ^^^ Interestingly , we find that certain S aryltryphostins discriminate between EGFR and HER 2 kinase in favor of the HER 2 kinase domain by almost 2 orders of magnitude . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
This protein was found to specifically stimulate the intrinsic tyrosine kinase activity of HER4 / p180erbB4 while having no direct effect on the phosphorylation of EGFR , HER 2 , or HER 3 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Receptor phosphorylation was also observed with the cell lines transfected with Her 2 or a chimeric receptor consisting of the extracellular domain of Her 2 and the transmembrane and cytoplasmic domains of epidermal growth factor receptor . ^^^ ErbB receptor activation , cell morphology changes , and apoptosis induced by anti Her 2 monoclonal antibodies . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The overexpression of two members of the erbB oncogene family the epidermal growth factor receptor protein ( EGF R ) and the HER 2 / neu protein in breast cancer has been investigated by numerous authors . ^^^ The simultaneous investigation of EGF R and HER 2 / neu in the same study population has only rarely been performed in breast cancer . ^^^ Therefore , we analyzed the EGF R and the HER 2 / neu protein expression in 142 breast cancer specimens and 12 benign breast samples by immunohistochemistry . ^^^ Steroid hormone receptor expression and the expression of EGF R and HER 2 / neu seem to be two independent phenomena in our samples of breast cancer . ^^^ The simultaneous evaluation of EGF R and HER 2 / neu expression did not lead to new information of prognostic relevance . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The HER 2 cell membrane tyrosine kinase , a member of the epidermal growth factor receptor family that is the transcription product of the erbB2neu oncogene , and HER 3 , a receptor protein of the same family , are overexpressed in prostate cancer and prostatic intraepithelial neoplasia . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In a series of 70 patients with childhood medulloblastoma , we have used immunohistochemistry and Western blotting analysis to investigate the expression patterns of all four EGFR family members ( EGFR , HER 2 , HER 3 , and HER 4 ) and heregulin alpha , a ligand for the HER 3 and HER 4 receptors . ^^^ These data suggest the hypothesis that HER 2 HER4 receptor heterodimerization is of particular biological significance in this disease , and this report is the first to demonstrate potential clinical significance of EGFR family heterodimerization in human cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The overexpression in tumor cells of ( proto ) oncogenic receptor tyrosine kinases such as epidermal growth factor receptor ( EGFR ) or ErbB2 / neu ( also known as HER 2 ) is generally thought to contribute to the development of solid tumors primarily through their effects on promoting uncontrolled cell proliferation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Cells were transfected with human platelet derived growth factor receptor ( PDGF R ) , macrophage colony stimulating factor 1 receptor ( CSF 1R ) , epidermal growth factor receptor ( EGF R ) , and chimeras consisting of the extracellular domain of EGF R and the transmembrane and cytoplasmic domains of either HER 2 ( HER 1 2 ) or c kit ( EK R ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We examined 23 breast tumors and 16 lung tumors , where the genes HER 1 coding for the epidermal growth factor receptor ( EGFR ) and HER 2 coding for p185HER 2 were analysed . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We also demonstrated that HRG stimulation promoted physical interactions between PAK 1 , actin , and human epidermal growth factor receptor 2 ( HER 2 ) receptors , and these interactions were dependent on the activation of PI 3 kinase . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Tumors that overexpress HER 2 / neu receptor or exhibit enhanced EGFR signaling have been reported to possess constitutively activated Src family kinases , especially pp60c Src . ^^^ High levels of pp60c Src activity have also been reported for cell lines that overexpress the EGFR or the chimeric EGFR HER 2 receptor . ^^^ In this study we show that the induced expression of c SRC antisense RNA or the application of a selective Src kinase inhibitor induces growth arrest , programmed cell death and reverses the transformed properties of cells that overexpress EGFR or HER 2 receptors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
HER 2 is a ligand less member of the human epidermal growth factor receptor or ErbB family of tyrosine kinases . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Human epidermal growth factor receptor 2 ( HER 2 ) is a member of the epidermal growth factor receptor family , which produces factors that are considered to be important mediators of cell growth . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In this study frozen sections of 19 ovarian cancers ( 2 stage 1 , 10 stage 3 , 2 stage 4 , and 5 recurrent ) , as well as 29 normal tissues , were evaluated by immunohistochemistry using 11 distinct MAbs against HER 2 / p185 and 2 antibodies against EGF R / p170 to assess coexpression of these receptors . ^^^ Staining of 273 specimens from 29 normal tissues indicated that coexpression of HER 2 and EGF R is rare . ^^^ These data confirm that HER 2 and EGF R are more frequently expressed in advanced ovarian cancers than in normal ovarian epithelium and a significant fraction of these tumors coexpress both HER 2 and EGF R . . ^^^ Coexpression of the HER 2 gene product , p185HER 2 , and epidermal growth factor receptor , p170EGF R , on epithelial ovarian cancers and normal tissues . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
There is now evidence that the actions of chemotherapy may involve Ras , tyrosine kinases ( epidermal growth factor receptor , HER 2 ) , TC 21 , or similar molecules . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Amplification of the human epidermal growth factor receptor 2 protein ( HER 2 ) in primary breast carcinomas has been shown to correlate with poor clinical prognosis for certain patients . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Furthermore , the levels of paxillin expression were closely linked with the coexpression of human epidermal growth factor receptor 2 ( HER 2 ) / HER3 receptors in breast cancer cell lines and in grade 3 human breast tumors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The compounds were further evaluated for their ability to inhibit the growth of cell lines that overexpress EGF R or HER 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Combination of EGFR , HER 2 / neu , and HER 3 is a stronger predictor for the outcome of oral squamous cell carcinoma than any individual family members . ^^^ In a series of 111 patients with squamous cell carcinoma ( SCC ) , we used immunohistochemistry to examine the expression levels of four epidermal growth factor receptor ( EGFR ) family members ( EGFR , HER 2 / neu , HER 3 , and HER 4 ) . ^^^ The expression of all EGFR members was significantly associated with shortened patient survival , and the association was strongest for HER 2 / neu . ^^^ Furthermore , the combination of HER 2 , HER 3 , and EGFR but not HER 4 significantly improved the predicting power . ^^^ The expression level of HER 2 / neu was significantly correlated with that of EGFR or HER 3 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
OBJECTIVE : To determine the influence of receptor tyrosine kinases , which are both expressed in pulmonary carcinomas and in human skin , we performed expression studies on epidermal growth factor receptor ( EGFR ) , HER 2 , HER 3 in a skin sample of tripe palms obtained from a patient with non small cell lung cancer with lymph node involvement . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The HER 2 / neu oncogene is localized to chromosome 17q and shares significant homology with the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The ability of the epidermal growth factor receptor ( EGFR ) family members , EGFR , HER 2 , HER 3 , and HER 4 , to form homo and heterodimers after interaction with different ligands expands the signal diversity of these proteins . ^^^ Consistently the predominant interaction after EGF treatment was between EGFR and HER 2 , whereas activation of HER 3 and HER 4 depended on the relative abundance of the four receptors in the cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Human epidermal growth factor receptor 2 ( HER 2 ) is overexpressed , usually as a result of HER 2 proto oncogene amplification , in 20 30 % of breast cancers . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The human epidermal growth factor receptor ( HER ) family consists of four distinct receptors : HER 1 ( epidermal growth factor receptor ) , HER 2 , HER 3 , and HER 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Oncogenic epidermal growth factor receptor family members , including EGFRvIII and HER 2 , are expressed in a broad spectrum of human malignancies . ^^^ Cell lines transfected with EGFRvIII and HER 2 are more resistant to paclitaxel mediated cytotoxicity , and tubulin polymerization induced by paclitaxel is suppressed compared with cells expressing wild type epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The percentages of biomarker expression for primary and metastatic lesions , respectively , were MDR 1 , 12 and 10 % ; p 53 , 55 and 60 % ; HER 2 , 12 and 11 % ; EGF R , 26 and 33 % ; increased microvessel counts ( CD 31 ) , 21 and 36 % . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Coexpression patterns of EGFR , HER 2 , HER 3 and HER 4 in non melanoma skin cancer . ^^^ The receptor tyrosine kinases ( RTKs ) epidermal growth factor receptor ( EGFR ) , HER 2 , HER 3 and HER 4 are involved in the pathogenesis of multiple human malignant neoplasias . ^^^ EGFR and HER 3 were predominantly expressed in the BCCs and SCCs , while HER 2 was ubiquitously expressed . ^^^ These results confirm this concept : isolated HER 2 expression and EGFR / HER2 were predominantly found in normal skin , while HER2 / HER3 and the triple expression of EGFR / HER2 / HER3 were seen more frequently in the BCCs and SCCs compared with normal skin ( 50 % and 40 % compared with 26 % , respectively ) . ^^^ The activation of HER 3 , in addition to EGFR and HER 2 , might therefore be associated with the malignant phenotype . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
HER 2 , a tyrosine kinase membrane receptor of the epidermal growth factor receptor family , has been the most widely studied marker in this respect . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In summary , monoclonal antibodies directed at two of the class 1 growth factor receptors , EGFR and HER 2 , have shown to be active and well tolerated . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
This growth factor mediated hnRNP K expression was effectively blocked by pretreatment of cultures with humanized anti EGF receptor ( EGFR ) antibody C 225 , or anti human epidermal growth factor receptor 2 ( HER 2 ) antibody . ^^^ These results suggested that the activity of human EGF receptor family members regulates hnRNP K expression by extracellular growth promoting signals and that therapeutic humanized antibodies against EGFR and HER 2 can effectively block this function . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Our understanding of the normal signaling mechanisms and functions of human epidermal growth factor receptor 2 ( HER 2 ) and other members of the HER family , namely epidermal growth factor receptor , HER 3 , and HER 4 , is growing rapidly . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Segment specific c ErbB 2 expression in human autosomal recessive polycystic kidney disease . c ErbB 2 ( also referred to as Neu or HER 2 ) , a transmembrane glycoprotein with intrinsic tyrosine kinase activity , is structurally related to epidermal growth factor receptor ( EGFR ) and forms active heterodimers with EGFR as well as other members of the EGFR family . c ErbB 2 is reported to mediate differentiation and proliferation in epithelial cells and is expressed in a tissue specific and developmental stage specific manner . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The human epidermal growth factor receptor HER 2 or C erbB 2 / neu is a tyrosine kinase membrane receptor , which when activated , induces a phosphorylation cascade in cytoplasmic kinases leading to increased protein transcription and cellular growth . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The product of the HER 2 / neu proto oncogene , HER 2 , is the second member of the human epidermal growth factor receptor ( HER ) family of tyrosine kinase receptors and has been suggested to be a ligand orphan receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Since the EGFR and HER 2 were recently identified as critical players in the transduction of signals by a variety of cell surface receptors , such as G protein coupled receptors and integrins , our special focus is the mechanisms and significance of the interconnectivity between heterologous signalling systems . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The HER 2 oncogene and its relative oncoprotein , gp185HER2 , a transmembrane glycoprotein belonging to the epidermal growth factor receptor family , are overexpressed in a wide range of solid tumors including breast and ovarian cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
HER 2 is a ligand less tyrosine kinase receptor of the ErbB family that is frequently overexpressed in breast cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
HER 2 , epidermal growth factor receptor ( EGFR ) , and p 53 have all been suggested as possible markers of tamoxifen resistance . ^^^ The aim of this study was to investigate interactions between adjuvant treatment with tamoxifen and the content of EGFR , HER 2 , and p 53 in steroid receptor positive patients . ^^^ The content of the steroid receptors and expression of p 53 , EGFR , and HER 2 were determined by immunohistochemical analysis of paraffin embedded tissue . ^^^ RESULTS : Multivariate analysis demonstrated no increased risk of recurrence after treatment with tamoxifen for HER 2 , EGFR , and p 53 positive , high risk , steroid receptor positive patients . ^^^ Patients with steroid receptor positive tumors and positive immunohistochemical staining for HER 2 , EGFR or p 53 benefited from treatment with tamoxifen for 1 year , although the latter variable contained independent prognostic information by itself . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The current study focuses on the generation of CTL and Th cells against the tumor associated Ag HER 2 using autologous dendritic cells ( DC ) derived from CD 34 ( + ) hematopoietic progenitor cells which have been retrovirally transduced with the human epidermal growth factor receptor 2 ( HER 2 ) gene . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
However , ER positive breast tumors overexpressing EGF R and / or HER 2 ( Erb B 2 ) are resistant to endocrine therapy . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
BACKGROUND : The human epidermal growth factor receptor 2 protein ( HER 2 ) signaling in breast cancer imparts a metastatic advantage to the cell , likely by regulating gene expression . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Substituted 4 ( 3 bromophenylamino ) quinazolines as putative irreversible inhibitors of the epidermal growth factor receptor ( EGFR ) and human epidermal growth factor receptor ( HER 2 ) tyrosine kinases with enhanced antitumor activity . ^^^ A series of new 6 substituted 4 ( 3 bromophenylamino ) quinazoline derivatives that may function as irreversible inhibitors of epidermal growth factor receptor ( EGFR ) and human epidermal growth factor receptor ( HER 2 ) tyrosine kinases have been prepared . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
These targets include matrix metalloproteinases , the K ras oncoprotein , the tumor suppressor p 53 , HER 2 , epidermal growth factor receptor , and vascularendothelial growth factor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Growth inhibition of these tumor cell lines was associated with the dephosphorylation of EGFR , HER 2 , and HER 3 , accompanied by the loss of association of HER 3 with phosphatidylinositol 3 kinase , and down regulation of Akt activity . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
HER 2 is a member of the epidermal growth factor receptor ( EGFR ) family of tyrosine kinases and is involved in the growth , invasion , metastasis , and prognosis of breast cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The incidence of human epidermal growth factor receptor 2 ( HER 2 ) protein overexpression and its prognostic value are not well characterized in patients with prostate cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The frequency of expression was : EGFR ( 51 % ) , HER 2 ( 54 % ) , P HER 2 ( 48 % ) , HER 3 ( 48 % ) , HER 4 ( 57 % ) , heregulin ( 48 % ) , p 38 ( 17 % ) , MAPK ( 48 % ) . ^^^ There was evidence of associations among the coexpression of heregulin , EGFR , HER 2 , and HER 3 . ^^^ The expression of EGFR , HER 2 , heregulin , p 38 and MAPK was independent of age , tumor size , number of lymph nodes involved or hormone receptor status . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Screening a random peptide library displayed on phage as fusion to the major capsid protein pVIII identified a ligand binding the human epidermal growth factor receptor 2 ( HER 2 ) specifically . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In this study we describe detailed immunohistochemical analysis of nuclear and cytoplasmic STATs 1 and 3 expression in primary breast carcinomas and correlate this with EGFR , HER 2 , p 53 , ER , PR , p21 / waf1 , Bcl XL and Ki 67 expression . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Therapeutic approaches used to target the EGFR and its signal transduction cascade include ( 1 ) monoclonal antibodies ( eg , cetuximab [ IMC C 225 ] ) directed against the extracellular binding domain of the receptor ; and ( 2 ) trastuzumab , a monoclonal antibody binding to the HER 2 receptor ; immunotoxin conjugates use an antibody directed against EGFR joined to a cell toxin . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Six out of 11 human pancreatic cancer cell lines expressed all four epidermal growth factor ( EGF ) receptor family members ( HER 1 ( EGF R ) , HER 2 , HER 3 , and HER 4 ) , including Panc 89 cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Potential therapeutic agents include downregulators of c erb B 1 ( EGFR ) and B 2 ( HER 2 ) receptor expressions , inhibitors of tyrosine kinase and farnesylation , and activators of growth inhibitory / proapoptotic pathways . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Clinical trials in patients positive for HER 2 ( human epidermal growth factor receptor 2 ) show that trastuzumab is effective and well tolerated ; as a single agent second line or third line treatment , the drug produced durable tumour responses . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We show that a `` natural chaperone complex ' ' between HSP 110 and the intracellular domain ( ICD ) of human epidermal growth factor receptor 2 protein ( HER 2 ) / neu is formed by heat shock . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
High levels of HER 2 expression alter the ability of epidermal growth factor receptor ( EGFR ) family tyrosine kinase inhibitors to inhibit EGFR phosphorylation in vivo . ^^^ The epidermal growth factor receptor ( EGFR ) and HER 2 tyrosine kinases have been implicated in the development , progression , and severity of several human cancers and are attractive targets for therapeutic intervention . ^^^ SU 11925 was developed as a small molecule inhibitor of the tyrosine kinase activity of both EGFR and HER 2 . ^^^ In cellular assays , SU 11925 exhibited similar potency against EGFR and HER 2 , inhibiting EGF stimulated EGFR autophosphorylation in A 431 ( human epidermoid carcinoma ) cells with an IC ( 50 ) of 30 nM and HER 2 phosphorylation in SK OV 3TP5 ( human ovarian carcinoma ) cells with an IC ( 50 ) of 38 nM . ^^^ In contrast to its similar activity against the two targets in cellular assays , approximately 10 fold higher plasma concentrations of SU 11925 were required to inhibit HER 2 phosphorylation in HER 2 overexpressing tumors compared with EGFR phosphorylation in EGFR overexpressing tumors in vivo . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The HER 2 protein is encoded by the HER2 / neu gene and it is homologous to the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
For the treatment of patients with metastatic breast cancer by humanized anti human epidermal growth factor receptor type 2 ( HER 2 ) antibody ( trastuzumab ) , it is important to evaluate HER 2 status adequately . `` A guideline for HER 2 testing ' ' and `` HER 2 atlas ' ' produced by the `` Pathological committee for optimal use of trastuzumab ' ' are introduced in this report . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
BACKGROUND : Amplification of the human epidermal growth factor receptor 2 ( HER 2 ) gene and overexpression of the HER 2 protein have been associated with an unfavorable prognosis . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
BACKGROUND : Clinically , human epidermal growth factor receptor 2 ( HER 2 ) overexpression is associated with a faster rate of tumor growth and an increased rate of metastasis , and a patient who is HER 2 strongly positive tends to have a poor prognosis and a decreased disease free survival and overall survival ( OS ) time . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Syntheses and EGFR and HER 2 kinase inhibitory activities of 4 anilinoquinoline 3 carbonitriles : analogues of three important 4 anilinoquinazolines currently undergoing clinical evaluation as therapeutic antitumor agents . ^^^ The EGFR and HER 2 kinase inhibitory activities and the cell growth inhibition of the two series are compared with each other and with the clinical lead EKB 569 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
One such receptor is human epidermal growth factor receptor 2 ( HER 2 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Celecoxib , a selective cyclooxygenase 2 inhibitor , protects against human epidermal growth factor receptor 2 ( HER 2 ) / neu induced breast cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Antihuman epidermal growth factor receptor 2 ( HER 2 ) monoclonal antibody trastuzumab enhances cytolytic activity of class 1 restricted HER 2 specific T lymphocytes against HER 2 overexpressing tumor cells . ^^^ The monoclonal antibody trastuzumab ( Herceptin ) directed against the human epidermal growth factor receptor 2 ( HER 2 ) results in tumor regressions when administered to patients with HER 2 overexpressing breast cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In contrast , epidermal growth factor receptor ( Ab 528 ) antibody only blocked 10 20 % of E ( 2 ) induced Erk activation , suggesting that E ( 2 ) induced Erk activation is predominantly mediated through the secretion of HRG and activation of HER 2 by an autoctine / paracrine mechanism . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Rational design of 4 , 5 disubstituted 5 , 7 dihydro pyrrolo [ 2 , 3 d ] pyrimidin 6 ones as a novel class of inhibitors of epidermal growth factor receptor ( EGF R ) and Her 2 ( p 185 ( erbB ) ) tyrosine kinases . ^^^ These compounds selectively inhibit EGF R kinase activity at low nanomolar concentration and tyrosine autophosphorylation in cells expressing EGF R or Her 2 ( p 185 ( erbB ) ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In this paper EGF R , HER 2 and HER 3 receptors were tested as therapeutic targets of immunotoxins in human rhabdomyosarcoma . ^^^ Rhabdomyosarcoma cells were treated with indirect immunotoxins consisting in primary specific murine monoclonal antibodies recognizing EGF R , HER 2 and HER 3 followed by secondary F ( ab ' ) 2 antimouse immunoglobulin linked to saporin S 6 , a type 1 ribosome inactivating protein ( RIP ) from the seeds of Saponaria officinalis . ^^^ The indirect immunotoxin targeting EGF R caused a significant inhibition in cell growth and protein synthesis and a strong increase in apoptosis in rhabdomyosarcoma cells , whereas indirect immunotoxins against HER 2 and HER 3 were ineffective . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
HER 2 expression was assessed in bladder carcinoma metastases and the corresponding primary tumours , and subsequently compared with the EGFR expression . ^^^ HER 2 and EGFR expression was analysed by immunohistochemistry in formalin fixed , paraffin embedded tissues from 21 patients with metastatic bladder carcinoma . ^^^ Human epidermal growth factor receptor 2 , HER 2 , is overexpressed in various tumours , e . g . breast and bladder tumours . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Certain types of malignant tumors overexpress HER 2 , a transmembrane glycoprotein of the class 1 receptor tyrosine kinase erbB family . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The design of an orally active , irreversible inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor ( EGFR ) and the human epidermal growth factor receptor 2 ( HER 2 ) . ^^^ A series of of 6 , 7 disubstituted 4 anilinoquinoline 3 carbonitrile derivatives that function as irreversible inhibitors of EGFR and HER 2 kinases have been prepared . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : Trastuzumab combined with chemotherapy improves outcomes for women with human epidermal growth factor receptor 2 ( HER 2 ) overexpressing advanced breast cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
HER 2 , HER 3 , and epidermal growth factor receptor were detected in the androgen independent cell line 22Rv1 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We observed this beta glucan effect irrespective of antigen ( GD 2 , GD 3 , CD 20 , epidermal growth factor receptor , HER 2 ) , human tumor type ( neuroblastoma , melanoma , lymphoma , epidermoid carcinoma and breast carcinoma ) or tumor sites ( s . c . versus systemic ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The effects of the treatment on mRNA and protein levels of human epidermal growth factor ( EGF ) receptors ( EGFR and HER 2 ) in ovarian tumors were determined by RT PCR and immunoblotting . ^^^ Treatment with AN 207 significantly ( < 0 . 01 ) decreased the expression of mRNA for EGFR , and HER 2 by 27 and 34 % , respectively , as compared to controls and reduced the receptor protein levels of EGFR and HER 2 by 35 and 36 % , respectively ( < 0 . 05 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : Human epidermal growth factor receptor 2 ( HER 2 ) overexpression is associated with a more aggressive form of breast cancer that responds well to trastuzumab therapy . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
BACKGROUND : Trastuzumab ( Herceptin ) has clinical indication in association with paclitaxel ( Taxol ) for the treatment of human epidermal growth factor receptor 2 ( HER 2 ) expressing breast cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Among the most promising targets for therapy are members of the human epidermal growth factor receptor ( HER / ErbB ) family , particularly HER 1 and HER 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
HER 2 ( erbB2 / neu ) is a member of the erbB family of receptor tyrosine kinases and is involved in regulating the growth of several types of human carcinomas . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
EGFR expression levels and activation by ligand correlate with radioresistance , and exogenous HER 2 expression alters radiation response . ^^^ Preclinical studies of anti EGFR anti HER 2 antibodies , and kinase inhibitors that inhibit EGFR , both EGFR and HER 2 , or all 4 family members show potential for clinical radiosensitization . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : To evaluate the feasibility , toxicity , and efficacy of single agent monoclonal antibody therapy targeting the human epidermal growth factor receptor 2 ( HER 2 ) / neu receptor in ovarian and primary peritoneal carcinoma . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
There appear to be several different levels at which this cross talk may occur , including peptide growth factor signaling via the type 1 tyrosine kinase growth factor receptor family [ epidermal growth factor receptor ( EGFR ) and HER 2 ] , which may become up regulated during endocrine treatment , ultimately being harnessed by cells to allow them hormone independent growth . ^^^ Preclinical approaches that have shown promise include the use of EGFR tyrosine kinase inhibitors for hormone resistant breast cancer cells that are dependent on either EGFR or HER 2 signaling . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Among the last category , some are currently used in the treatment of patients , including 2 monoclonal antibodies targeting receptors with tyrosine kinase activity ( HER 2 : Herceptin ( DCI : trastuzumab ) , EGFr : Erbitux ( DCI : cetuximab ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Approximately 30 % of breast cancers overexpress HER 2 / neu , a member of the epidermal growth factor receptor family . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Trastuzumab is the first of these biologic therapies to be approved for patients with human epidermal growth factor receptor 2 ( HER 2 ) overexpressing metastatic breast cancer . ^^^ Small molecules that inhibit specific tyrosine kinases ( e . g . , epidermal growth factor receptor , HER 2 ) are in phase 1 and phase 2 clinical trials . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
However , multiple diverse mechanisms may be involved in these overall effects , including signaling by HER 2 itself , modulation of signaling by epidermal growth factor receptor ( EGFR ) , and modification of trafficking dynamics for both EGFR and HER 2 . ^^^ We then use our model for successful prediction of EGFR and HER 2 level and location changes attributable to HER 2 overexpression in 184A1 human mammary epithelial cells expressing a series of HER 2 levels by retroviral infection . ^^^ Model predictions are based on our independent experimental measurement of key trafficking parameters for both EGFR and HER 2 . ^^^ In terms of trafficking processes , HER 2 overexpression reduces the EGFR internalization rate constant and increases the fraction of EGFR recycled . ^^^ Consequently , our model successfully predicts that HER 2 increases the overall level of activated EGFR by both enhancing its recycling and reducing its internalization , but it increases activated EGFR localization at the cell surface almost solely by its reduction of internalization . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The results suggested that , along with PSA , PSM ( FOLH 1 ) , kallikrein 2 , and a 2 macroglobulin , cell signaling genes EGFR , HER 2 , HER 3 , TOP 2 , KRT 8 , KRT 18 , VEGF , CD 44 , VIM , CAV 1 , and CAV 2 may serve as diagnostic and prognostic markers in PC . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
This review describes the roles of HER 2 , epidermal growth factor receptor ( EGFR ) , oestrogen receptor ( ER ) / progesterone receptor ( PgR ) , Ki 67 , Bcl 2 , p 53 and gene expression profiling in predicting responses to endocrine , cytotoxic and biological therapies . ^^^ HER 2 already has an established role in this area , but the role of EGFR requires further elaboration . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
More broadly , recent clinical trials have confirmed improved survival with combinations of HER 2 ( a member of the ErbB family of receptors ) targeted antibodies and chemotherapy in patients with advanced breast cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The xenograft and cell line had retained a somatic TP 53 missense mutation ( S215I ) originating from the primary tumors , as well as a lack of immunohistochemically detectable expression of steroid hormone receptors , epidermal growth factor receptor , human epidermal growth factor receptor 2 ( HER 2 ) , and keratin 8 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Although RTKs are a large family , HER 2 , epidermal growth factor receptor ( EGFR ) , Met ( hepatocyte growth factor receptor ) , and others all have shown the ability to predict outcome . ^^^ Specifically , HER 2 and EGFR showed similar expression patterns ( P < 0 . 0001 ) , and Met cytoplasmic domain and FGFR cytoplasmic staining showed similar expression patterns ( P < 0 . 0001 ) , but no correlation was found between the two groups . ^^^ CONCLUSIONS : The current results indicate that the cytoplasmic domain of Met shows a unique staining pattern and defines a set of patients unique from the set of patients defined by overexpression of HER 2 , EGFR , or hormone receptors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The anticancer potential of curcumin stems from its ability to suppress proliferation of a wide variety of tumor cells , down regulate transcription factors NF kappa B , AP 1 and Egr 1 ; down regulate the expression of COX 2 , LOX , NOS , MMP 9 , uPA , TNF , chemokines , cell surface adhesion molecules and cyclin D 1 ; down regulate growth factor receptors ( such as EGFR and HER 2 ) ; and inhibit the activity of c Jun N terminal kinase , protein tyrosine kinases and protein serine / threonine kinases . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Eight biological markers were retrospectively assayed for most patients : estrogen ; progesterone ; prolactin receptors ( PrlRs ) ; microvessel count ( MVC ) ; S phase fraction ; tumor ploidy ; epidermal growth factor receptor ( EGFR ) ; and HER 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ZD 1839 , a specific epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor , induces the formation of inactive EGFR / HER2 and EGFR / HER3 heterodimers and prevents heregulin signaling in HER 2 overexpressing breast cancer cells . ^^^ Our aim was to explore the effects of ZD 1839 in breast cancer cell lines expressing different levels of EGFR and the closely related HER 2 receptor . ^^^ RESULTS : ZD 1839 was an equally potent inhibitor of growth in breast cancer cells expressing high levels of EGFR and HER 2 . ^^^ Because ZD 1839 does not inhibit the HER 2 tyrosine kinase in vitro , and because heregulin is a ligand that activates HER 2 by binding to HER 3 and HER 4 but does not bind to the EGFR , our findings suggested that ZD 1839 interfered with HER 2 function in intact cells . ^^^ CONCLUSIONS : ZD 1839 inhibits the growth of HER 2 overexpressing breast cancer cells , possibly by sequestration of HER 2 and HER 3 receptors in an inactive heterodimer configuration with the EGFR . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Many cell types express multiple EGFR family members ( including EGFR , HER 2 , HER 3 , and / or HER 4 ) that interact to form an array of homo and heterodimers . ^^^ Parameters characterizing EGFR and HER 2 interactions were determined using experimental data obtained from mammary epithelial cells constructed to express different levels of HER 2 , enabling us to estimate receptor specific internalization rate constants and dimer uncoupling rate constants . ^^^ Furthermore , model predictions of the relationship of HER 2 expression levels to consequent distribution of EGFR homodimers and EGFR / HER2 heterodimers suggest that the levels of HER 2 found on normal cells are barely at the threshold necessary to drive efficient heterodimerization . ^^^ Thus , altering HER 2 concentrations , either overall or local , could provide an effective mechanism for regulating EGFR / HER2 heterodimerization and may explain why HER 2 overexpression found in some cancers has such a profound effect on cell physiology . . ^^^ Quantitative analysis of HER 2 mediated effects on HER 2 and epidermal growth factor receptor endocytosis : distribution of homo and heterodimers depends on relative HER 2 levels . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Her 2 / neu / c erbB 2 , a member of the epidermal growth factor receptor family , can be cleaved into a soluble extra cellular domain ( ECD ) and a membrane bound stub fragment . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The epidermal growth factor receptor HER 2 is not a major therapeutic target in Ewing sarcoma . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The EGF Receptor ( EGFR ) , the first transmembrane receptor tyrosine kinase cloned and sequenced , and its closely related family members HER 2 , HER 3 , and HER 4 , play myriad roles in mammalian growth and development . ^^^ This signaling system ' s impact on human neoplasia is underscored by the following : i . ) EGFR is overexpressed or activated by autocrine or paracrine growth factor loops in at least 50 % of epithelial malignancies ; ii . ) HER 2 is amplified and dramatically overexpressed in approximately 20 % 25 % or breast cancers ; 3 ) HER 3 and HER 4 are variably expressed in breast and other cancers . ^^^ Overexpression and / or activation of EGFR , HER 2 and HER 3 has been correlated with poor tumor prognosis ; antibody and small molecule inhibitors of their activity are being tested as therapy in cancer patients . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
EGFR and Her 2 are overexpressed in lung cancers and have , therefore , been chosen as preferred targets for novel therapies . ^^^ These findings prompted us to re visit the oncogenic pathways , which play a role in lung cancers , with special emphasis on the way EGFR / Her 2 signaling cooperates with other signaling pathways . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In the present study , we examined surgically obtained specimens from a series of 36 NSCLC patients for expression of EGFR , phosphorylated EGFR ( p EGFR ) , and HER 2 by immunohistochemistry , and also examined the correlation with clinical characteristics . ^^^ The positive rate of EGFR , p EGFR , and HER 2 was 97 . 2 % , 44 . 4 % , and 88 . 6 % , respectively , and the overexpression rate was 80 . 6 % , 0 . 0 % , and 27 . 8 % , respectively . ^^^ EGFR overexpression and phosphorylation were seen at almost the same rate in each histological type of squamous and nonsquamous cell carcinoma ( squamous vs . nonsquamous ; 78 . 6 % vs . 81 . 8 % for EGFR , 35 . 7 % vs . 50 . 0 % for p EGFR ) , while HER 2 overexpression was seen less frequently in squamous cell carcinoma than in nonsquamous cell carcinoma ( 0 . 0 % vs . 45 . 5 % , P = 0 . 003 ) . ^^^ EGFR phosphorylation was correlated to short time to progression ( TTP ) ( P = 0 . 002 ) and poor prognosis ( P = 0 . 002 ) , although EGFR overexpression , HER 2 overexpression , or EGFR HER 2 coexpression were not correlated to TTP or survival . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
INTRODUCTION : The human epidermal growth factor receptor ( her 2 / neu ) protooncogene encodes a membrane tyrosine kinase with homology to the epidermal growth factor receptor ( EGFR ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In such tumors , HER 2 functions as a preferred coreceptor to form heterodimers with HER 1 ( EGFR ) , HER 3 or HER 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : Human epidermal growth factor receptor 2 ( HER 2 ) overexpression was found to predict a good response in breast carcinoma patients treated with doxorubicin ( Adriamycin [ ADM ] ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The Erb B family of receptors plays an important role in lung carcinogenesis and tumor development , and EGFR and HER 2 are highly expressed in bronchial preneoplasia . ^^^ In invasive tumors , EGFR are expressed in 50 90 % , and mostly in squamous cell carcinomas , but also in adenocarcinomas and large cell carcinomas , while HER 2 is less frequently expressed ( 20 30 % ) and mostly expressed in adenocarcinomas . ^^^ The genetic mechanisms responsible for overexpression of EGFR and HER 2 proteins might be numerous , including gene dosage ( overrepresentation or amplification ) as well as translational and post translational mechanisms . ^^^ However , for EGFR and HER 2 there is a positive correlation between gene copy numbers and level of protein expression demonstrated by fluorescence in situ hybridization analysis and immunochemistry . ^^^ Gene amplification for EGFR and HER 2 is demonstrated in only 5 10 % of the tumors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In addition to Herceptin , a large number of various HER 2 directed immunological and genetic approaches , either targeting the HER 2 receptor , its signaling pathways or both HER 2 and epidermal growth factor receptor ( EGFR ) together , have demonstrated promising pre clinical potential towards HER 2 amplified carcinomas . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In contrast to epidermal growth factor receptor or HER 2 , the kinasedeficient HER 3 self associates readily at low nanomolar concentrations and in the absence of its ligands , various isoforms of heregulin ( hrg ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : Trastuzumab based therapy improves survival for women with human epidermal growth factor receptor 2 ( HER 2 ) positive advanced breast cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In this issue , researchers describe a simple assay for the rapid , high throughput identification of novel agents that promote degradation of the kinases Her 2 and EGFR . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Microtiter cell based assay for detection of agents that alter cellular levels of Her 2 and EGFR . ^^^ Overexpression of the transmembrane tyrosine kinases Her 2 and EGFR is associated with aggressive malignancies , and several therapeutic strategies targeting the two receptors are now in various stages of clinical development . ^^^ Here , we report the development of a microtiter cell based assay that sensitively detects cellular levels of Her 2 and EGFR . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Trastuzumab is the first agent that has been approved for patients with human epidermal growth factor receptor 2 ( HER 2 ) overexpressing breast cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Prognostic significance of EGFR and Her 2 in oral cavity cancer in betel quid prevalent area cancer prognosis . ^^^ Although several studies have found overexpression of epidermal growth factor receptor ( EGFR ) proteins EGFR and Her 2 in head and neck cancers , the clinical relevance of the finding varies . ^^^ EGFR and Her 2 proteins were measured in 59 paired ( grossly normal and cancer ) tissues by an enzyme immunoassy method . ^^^ Of the patients assayed , 34 ( 58 % ) and 24 ( 41 % ) had EGFR and Her 2 overexpression , with average 3 . 5 and 1 . 5 fold elevations . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Testing for epidermal growth factor receptor in lung cancer : have we learned anything from HER 2 testing . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
These results , taken together with previous evidence that EGCG also inhibits activation of the EGFR in carcinoma cells , suggest that EGCG may be useful in treating cases of breast carcinoma and HNSCC in which activation of the EGFR and / or HER 2 plays important roles in tumor survival and growth . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
BACKGROUND : This study prospectively examines the prognostic role of p 53 oncoprotein ( p 53 ) , Ki 67 antigen ( Ki 67 ) , tumor angiogenesis ( MVD ) , epidermal growth factor receptor ( EGFR ) , and HER 2 receptor protein ( HER 2 ) expression in Chinese with undifferentiated nasopharyngeal carcinoma ( NPC ) . ^^^ Prognostic significance of tumor angiogenesis , Ki 67 , p 53 oncoprotein , epidermal growth factor receptor and HER 2 receptor protein expression in undifferentiated nasopharyngeal carcinoma a prospective study . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The HER2 / neu gene encodes a 185 kDa transmembrane receptor ( HER 2 ) that belongs to the epidermal growth factor receptor family and has intrinsic tyrosine kinase activity . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
A strategy of full site occupancy and stereospecific recognition in the triphosphate subsite was used to specifically inhibit two protein kinases HER 2 and HER 4 from the EGFR family . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : This phase 2 study evaluated the pharmacokinetics and safety of trastuzumab and paclitaxel given every 3 weeks to women with human epidermal growth factor receptor 2 ( HER 2 ) overexpressing metastatic breast cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The sensitivity of lung cancer cell lines to the EGFR selective tyrosine kinase inhibitor ZD 1839 ( ' Iressa ' ) is not related to the expression of EGFR or HER 2 or to K ras gene status . ^^^ In addition , ZD 1839 sensitivity was not associated with expression of human epidermal growth factor receptor 2 ( HER 2 ) , another member of this tyrosine kinase receptor family nor with co expression of EGFR and HER 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Receptor guided alignment based comparative 3D QSAR studies of benzylidene malonitrile tyrphostins as EGFR and HER 2 kinase inhibitors . ^^^ The overexpression and / or mutation of the epidermal growth factor receptor family of tyrosine kinases , namely EGFR and HER 2 , have been implicated in poor prognosis of human solid tumors and are under investigation as molecular targets for cancer therapy . ^^^ In the EGFR kinase results , alignments 1 and 2 produced comparable 3D QSAR models with alignment 2 being slightly better than 1 , whereas in the HER 2 results , alignment 1 was better than alignment 2 in its predictive ability . ^^^ It appears that differences in binding mode preferences at the ATP site might constitute a reason for the selectivity of the dihydroxy compounds as inhibitors of EGFR relative to HER 2 . ^^^ They are more likely to have multiple binding modes at the ATP site of EGFR , i . e . , either modes A or B , than in the ATP site of HER 2 where they are possibly limited to only binding mode , A . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
SUMMARY : BACKGROUND Over expression of the human epidermal growth factor receptor 2 ( Her 2 ) protooncogene is associated with poor prognosis among female patients with breast cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
However , the metastasis selected variants showed no increases in expression of the growth factor receptors EGFR or HER 2 , and the pro angiogenic factors VEGF A and IL 8 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We also evaluated whether AN 152 can affect mRNA expression of human epidermal growth factor receptor and HER 2 and 3 oncogenes RESULTS : After 32 days of treatment with AN 152 , the growth of LNCaP cancers in castrated nude mice was strongly inhibited by 83 % versus intact controls ( P < 0 . 01 ) and 62 % versus castrated controls ( P < 0 . 05 ) . ^^^ The inhibition of MDA PCa 2b tumors by AN 152 was associated with a significant decrease in mRNA expression for epidermal growth factor receptor , HER 2 , and 3 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Association between the survival time and high expression of EGFR and HER 2 in breast cancer ] . ^^^ OBJECTIVE : To investigate the relationship between the survival time and the high expression of epidermal growth factor receptor ( EGFR ) and human epidermal receptor 2 ( HER 2 ) in breast cancer patients , and assess the feasibility of using the two markers either alone or in combination for predicting the prognosis of the patients . ^^^ METHODS : Breast cancer samples were obtained from 185 patients and measured for the expressions of EGFR and HER 2 by way of immunohistochemistry , and 120 patients ( 64 . 9 % ) were followed up and their survival time recorded . ^^^ Positive HER 2 expression was detected in 57 . 8 % and EGFR expression in 40 . 5 % of the all the samples examined . ^^^ The over expression of either HER 2 or EGFR was in inverse correlation with the survival time ( P < 0 . 05 and P < 0 . 01 , respectively ) , and the over expression of both related to the survival time in similar manner ( P < 0 . 05 and P < 0 . 01 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We investigated the role of the PEST type protein tyrosine phosphatase BDP 1 in the regulation of HER 2 , a member of the epidermal growth factor receptor ( EGFR ) family of RTKs . ^^^ Overexpression of BDP 1 inhibited ligand induced activation of HER 2 but not that of the closely related EGFR . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Since cytoplasmic HER 2 is incapable of transmitting the strong mitogenic signal via heterodimerization with other members of the Epidermal Growth Factor Receptor ( EGFR ) family , this may partly explain the correlation between cytoplasmic HER 2 over expression and a better prognosis in the Dukes ' C colorectal cancers . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Proliferation , survival , and activation of Akt and MAPK were evaluated in six human breast cancer cell lines expressing various levels of EGFR and HER 2 and exposed to ZD 1839 . ^^^ EGFR and HER 2 expression levels were determined using specific monoclonal antibodies and FACS analysis . ^^^ The effects of ZD 1839 were independent of EGFR expression levels , but were influenced by high HER 2 expression . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunohistochemical double staining with estrogen receptor ( ER ) and epidermal growth factor receptor 2 ( HER 2 ) was conducted in tissue sample of 125 women with invasive breast cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
BACKGROUND : Since the clinical introduction of trastuzumab ( Herceptin ) for metastatic breast cancers that overexpress human epidermal growth factor receptor 2 ( HER 2 ) , this anticancer agent has played an important role in breast cancer treatment . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The survival benefit with anastrozole or exemestane in advanced breast cancer , or with the addition of trastuzumab to standard chemotherapy in metastatic breast cancer that overexpresses human epidermal growth factor receptor 2 ( HER 2 ) , is approximately 4 to 5 months . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
HER 2 is a member of the human epidermal growth factor receptor family , possessing protein kinase activity in its cytoplasmic domain . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Because neoadjuvant trials permit temporal sampling of breast tissue , substudies in the phase 3 trial with letrozole have examined the impact of such biomarkers as estrogen receptor , progesterone receptor and epidermal growth factor receptor family members , HER 1 and HER 2 , on patient response . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
However , only the cell lines that were dependent on autocrine EGFR mediated cell proliferation were susceptible to the antiproliferative and antitumorigenic effects of HER 2 inhibition . ^^^ The relative levels of HER 2 , EGFR , HER 3 and HER 4 were not predictive of responsiveness to mAb 4D5 . ^^^ Treatment with HER 2 antibodies caused a decrease in HER 2 protein levels in all of the colon cancer cell lines and also significantly decreased EGFR levels but only in the EGFR dependent cell lines . ^^^ Combined inhibition of HER 2 and EGFR caused large areas of necrosis in EGFR dependent colon cancer xenografts , suggesting a benefit of combined HER 2 and EGFR inhibitor therapy . ^^^ Predicting clinical responsiveness of human colon cancer cells to anti HER 2 and anti EGFR therapy may require demonstration of EGFR tyrosine kinase dependency of the cells . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Biomarker profiles ( p 53 , Her 2 neu , and EGFR ) were also evaluated to determine if their expression patterns were associated with histology . ^^^ With respect to biomarker profiles , mP 53 was detected in 46 % , Her 2 neu in 16 % , and EGFR in 30 % of the cases evaluated . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Effects of the EGFR / HER2 kinase inhibitor GW 572016 on EGFR and HER 2 overexpressing breast cancer cell line proliferation , radiosensitization , and resistance . ^^^ PURPOSE : Two members of the epidermal growth factor receptor family , EGFR and HER 2 , have been implicated in radioresistance in breast cancer and other malignancies . ^^^ To gauge the potential clinical utility of targeting both EGFR and HER 2 to control growth and radiosensitize human breast cancers , we examined the effect of a dual EGFR / HER2 inhibitor , GW 572016 , on the proliferation and radiation response of either EGFR or HER 2 overexpressing human breast cancer cell lines . ^^^ METHODS AND MATERIALS : Primary human breast cancer cell lines that endogenously overexpress EGFR or HER 2 and luminal mammary epithelial H16N2 cells stably transfected with HER 2 were evaluated for the effect of GW 572016 on inhibition of ligand induced or constitutive receptor phosphorylation , proliferation , radiosensitization , and inhibition of downstream signaling . ^^^ RESULTS : GW 572016 inhibited constitutive and / or ligand induced EGFR or HER 2 tyrosine phosphorylation of all five cell lines , which correlated with the antiproliferative response in all but one cell line . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Treatment of SKRC 49 with 1 micro M ZD 1839 resulted in a marked decrease in the phosphorylation of EGFR but not of HER 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Agents that have only begun to undergo clinical evaluation include CI 1033 , an irreversible pan erbB tyrosine kinase inhibitor , and PKI 166 and GW 572016 , both examples of dual kinase inhibitors ( inhibiting epidermal growth factor receptor and Her 2 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Human epidermal growth factor receptor ( HER 2 ) is amplified in 25 to 30 % of breast cancer patients and those whose tumors demonstrate HER 2 gene amplification and protein overexpression have an inferior prognosis manifested by shorter disease free and overall survival . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We have examined overexpression of the human epidermal growth factor receptor 2 ( HER 2 ) to determine if it modifies the anti proliferative effect of transforming growth factor ( TGF ) beta against MCF 10A human mammary epithelial cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
To evaluate this concern , we prepared a single TMA block from 125 invasive breast carcinomas collected in a population based case control study conducted in Poland and compared estrogen receptor ( ER alpha ) , progesterone receptor ( PR ) , and human epidermal growth factor receptor 2 ( HER 2 ) expression in sections cut and stored for 6 months at room temperature with sections cut from the same TMA block and stained on the same day . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The various cell lines expressed different levels of EGFR , HER 2 , HER 3 , and HER 4 , but there was no correlation between levels of EGFR and / or HER 2 expression and drug sensitivity . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
BACKGROUND : We have shown previously that whereas overexpression of human epidermal growth factor receptor ( HER ) 1 , HER 2 and HER 3 is associated with poor prognosis in breast cancer , HER 4 is associated with a good prognosis . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
One reason for the low median survival rate may be intense cross talk between growth factor receptors such as the epidermal growth factor receptor ( EGFR / HER1 ) and the HER 2 growth factor receptor . ^^^ Thus , for patients with MBC whose tumors co express EGFR and HER 2 , gefitinib in combination with trastuzumab may prevent receptor cross talk , improving the outcome of MBC . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
This investigation is beginning to elucidate the influence of growth factor pathways that interact with the ER , especially HER 1 ( epidermal growth factor receptor [ EGFR ] ) and HER 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Overexpression of EGFR and HER 2 is frequently found in non small cell lung cancer ( NSCLC ) , which accounts for over 80 % of all malignant lung tumors , and has been associated with a worse clinical outcome . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The multichaperone heat shock protein ( Hsp ) 90 complex mediates the maturation and stability of a variety of proteins , many of which are crucial in oncogenesis , including epidermal growth factor receptor ( EGF R ) , Her 2 , AKT , Raf , p 53 , and cdk 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Adding trastuzumab to these cytotoxic agents can improve outcome for women with human epidermal growth factor receptor 2 ( HER 2 ) overexpressing advanced breast cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
ER hormone responsiveness is widely believed to be influenced by enhanced cross talk of ER with overexpressed human epidermal growth factor receptor 2 ( HER 2 ) , and a subgroup of ER positive tumors coexpress high HER 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Two protooncogene products , EGFR ( Her 1 , c erbB 1 ) and HER 2 ( Her 2 / neu , c erbB 2 ) , have been reported to be frequently overexpressed in head and neck squamous cell carcinoma ( HNSCC ) . ^^^ In order to identify patients who may benefit from targeted cancer treatment for these two molecules , we determined the expression status of EGFR and HER 2 in 129 HNSCC tumor specimens . ^^^ Two pharmacodiagnostic kits ( EGFR pharmDx and HercepTest ) were used to identify HNSCC tumors that overexpress EGFR or HER 2 . ^^^ Overexpression of EGFR was detected in 42 . 6 % of the tumor specimens , while HER 2 was only rarely expressed ( overexpression was observed in just 3 . 1 % of all cases ) . ^^^ Given the necessity of new therapeutic modalities for patients suffering from HNSCC , treatment EGFR signaling inhibitors appears to be warranted , whereas therapeutic intervention with HER 2 inhibitors seems to be inappropriate in this tumor type . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The predictive value of Human Epidermal growth factor Receptor 2 ( HER 2 ) on the response to chemotherapy and endocrine therapy in breast cancer patients has not yet been determined . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In addition , we did not find any difference in TTP , OS , toxicity , and symptom outcome in the group of patients overexpressing both HER 2 and EGFR compared with patients who had no overexpression of HER 2 CONCLUSION : According to these data , efficacy , toxicity , and symptom outcome in patients with NSCLC treated with gefitinib do not seem to be related to HER 2 expression . . ^^^ Gefitinib in pretreated non small cell lung cancer ( NSCLC ) : analysis of efficacy and correlation with HER 2 and epidermal growth factor receptor expression in locally advanced or metastatic NSCLC . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
AIMS AND BACKGROUND : The human epidermal growth factor receptor 2 ( HER 2 ) protein is a unique and useful target for antibody therapy against breast cancers that overexpress the HER 2 / neu gene . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The human epidermal growth factor Receptor 2 ( HER 2 ) seems to play an important role in the development of this neoplasia , and genetic alterations in this gene , such as point mutations and polymorphisms have been detected in breast cancer patients . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In many cell types , depletion of cholesterol activates signaling proteins like epidermal growth factor receptor ( EGFR ) , human epidermal growth factor receptor 2 ( HER 2 ) , or extracellular signal regulated kinase ( ERK ) known to affect cell differentiation . ^^^ MbetaCD treatment induces phosphorylation of EGFR , HER 2 , and ERK , but not HER 3 . ^^^ Inhibition of EGFR with PD 153035 impairs the MbetaCD induced phosphorylation of EGFR , HER 2 , and ERK , but does not impair the alteration of K 14 , K 10 , or involucrin gene expression , indicating that other signaling proteins regulate this phenomenon . p 38 has been suggested to regulate the expression of involucrin during keratinocyte differentiation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The aim of the study was to investigate the relationship between the expression of human epidermal growth factor receptor 2 ( HER 2 ) and activator protein 2 ( AP 2 ) , as well as the prognostic significance of HER 2 in breast cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
METHODS : MCF 7 breast cancer cells , which express high levels of AIB 1 , and a tamoxifen resistant derivative cell line engineered to overexpress HER 2 ( MCF 7 / HER2 18 ) were treated with estrogen , tamoxifen , epidermal growth factor ( EGF ) , or heregulin in the absence or presence of the EGF receptor ( EGFR ) tyrosine kinase inhibitor gefitinib . ^^^ Molecular cross talk between the ER and HER 2 pathways was increased in the MCF 7 / HER 2 cells compared with MCF 7 cells , with cross phosphorylation and activation of both the ER and the EGFR / HER2 receptors , the signaling molecules AKT and ERK 1 , 2 mitogen activated protein kinase ( MAPK ) , and AIB 1 itself with both estrogen and tamoxifen treatment . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
This retrospective study aimed at evaluating the prognostic impact of high serum levels of either the HER 2 extracellular domain ( ECD ) or the epidermal growth factor receptor ( EGFR ) ECD measured using two specific ELISAs in 221 patients with non small cell lung cancer ( NSCLC ) receiving conventional therapy and 41 nonmalignant pulmonary diseases patients . ^^^ It was not possible to discriminate between lung cancer and benign lung disease owing to the lack of sensitivity specificity relationship of HER 2 and EGFR ECD levels . ^^^ Neither HER 2 nor EGFR ECD specific levels were associated with a particular prognosis of NSCLC patients receiving conventional therapy . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Thus , it has been demonstrated that the number of genes coding for the human epidermal growth factor receptor 2 ( HER 2 ) is increased in a number of breast tumors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Expression of EGFR , HER 2 and phosphorylated ERK1 / 2 were measured by immunoblotting in a panel of breast cancer cell lines . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Trastuzumab ( Herceptin ) is a recombinant humanised IgG 1 monoclonal antibody against the human epidermal growth factor receptor 2 ( HER 2 ) , used for metastatic breast cancer treatment . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In addition , immunohistochemical assessment of epidermal growth factor receptor ( EGFR ) , Her 2 , and proliferation by MIB 1 expression was performed on the same TMAs and the scores were compared with those of PTEN and pAKT . ^^^ No correlation was seen between either PTEN or AKT and EGFR , Her 2 or MIB 1 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
HER gene family ( HER 1 HER4 ) encodes structurally similar transmembrane proteins ( EGFR , HER 2 , ErB 3 , and ErB 4 ) with tyrosine kinase activity . ^^^ HER 2 and EGFR overexpression is detected in the cells of many tumours , mainly in breast , lung and oral cancer and may be connected with HER 2 gene amplification or point mutations as well as with the presence of overactive polymorphic forms of HER 1 gene . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Although EGFR is the preferred dimerization partner for HER 2 , it is unclear whether expression of these 2 interrelated receptors in a given patient with breast cancer would be parallel or mutually exclusive . ^^^ OBJECTIVES : To assess EGFR status in primary breast carcinoma versus metastatic central nervous system ( CNS ) sites and to compare results with HER 2 / neu status in the same tumor . ^^^ Additionally , EGFR and HER 2 / neu status were concordant among multiple CNS metastases per individual case in only 45 % of patients . ^^^ In our study , most metastatic tumor deposits showed expression for either EGFR or HER 2 / neu , and less often for both , implying that drug therapies could be individualized for patients based on test results for both receptors . . ^^^ Epidermal growth factor receptor and HER 2 / neu status were concordant at the primary site in only 45 % of patients . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Our results show that downregulation of endogenous Syk expression enhances the ligand induced activity of the epidermal growth factor receptor ( EGFR ) but not that of the closely related human epidermal growth factor receptor 2 ( HER 2 ) and human epidermal growth factor receptor 3 ( HER 3 ) receptors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : Preclinical data indicate that expression of the ErbB family of receptors , such as HER 2 and HER 1 ( EGFR ) may be involved in endocrine resistance . ^^^ CONCLUSION : Patients with HER 2 amplification and HER 1 expression had lower ER levels and were modestly less responsive to tamoxifen , suggesting that molecular events in addition to those involving the ErbB receptors are important in determining the endocrine resistant phenotype . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
HER 3 preferentially forms heterodimers with HER 2 inducing the most potent mitogenic signal among EGFR family members . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Expression levels of EGFR and Her 2 were assessed by immunohistochemical staining . ^^^ The staining for EGFR , Her 2 , and P Akt were related to outcome in the two groups . ^^^ In the first series of patients , 43 % were positive for EGFR , 5 % for Her 2 , and 82 . 6 % for P Akt . ^^^ Of the survivors , 25 % were positive for EGFR , 0 % for Her 2 , and 42 % for P Akt . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : We set out to evaluate alterations of the therapeutic target genes KIT ( CD 117 ) , EGFR , and HER 2 in human retinoblastoma . ^^^ Immunohistochemistry was performed to analyze the expression of CD 117 , EGFR , and HER 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We predicted these putative aberrant translation products from the cDNA of three tumor associated antigens ( Ag ) : a transmembrane glycoprotein of the class 1 receptor tyrosine kinase erbB family HER 2 , telomerase reverse transcriptase ( TERT ) and prostatic acid phosphatase ( PAP ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : The aim of this study was to assess serum extracellular binding domains of epidermal growth factor receptor ( EGFR ) and HER 2 as surrogate markers of Gefitinib ( Iressa , ZD 1839 , AstraZeneca , London , United Kingdom ) activity in patients with non small cell lung cancer . ^^^ EXPERIMENTAL DESIGN : Serum EGFR and HER 2 levels were monitored in blood samples taken within 1 week of starting Gefitinib at day 28 and at every computed tomography scan evaluation . ^^^ EGFR and HER 2 were assayed in duplicate using commercial sandwich enzyme linked immunosorbent assay kits ( Oncogene Science Bayer Corporation , Cambridge , UK ) . ^^^ A logistic regression analysis was performed to evaluate : ( 1 ) the relationship between best overall tumor response and basal EGFR and HER 2 levels , and ( 2 ) the association between best overall tumor response and the differences of EGFR and HER 2 levels obtained at the best overall tumor response and at baseline . ^^^ Median pretreatment EGFR and HER 2 were 83 . 3 ng / ml and 13 . 7 ng / ml . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
METHODS : Immunohistochemical staining was undertaken for estrogen ( ER ) and progesterone ( PR ) receptors , epidermal growth factor receptor 2 ( Her 2 ) , p 53 , vascular endothelial factor ( VEGF ) , and hypoxia inducible factor 1alpha ( HIF 1alpha ) and the levels of these markers was compared to e cadherin expression in a high risk African American patient population . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Trastuzumab ( Herceptin ) is a therapeutic monoclonal antibody specific for the human epidermal growth factor receptor type 2 ( HER 2 ) , a cell surface tyrosine kinase receptor overexpressed by 25 % to 30 % of breast cancers . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Further experiments to determine expression changes of the receptor tyrosine kinases HER 2 and epidermal growth factor receptor did not reveal any alterations in MCF 7 ( LT ) if compared to wild type cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Multiple different oncogenes have been described previously to be amplified in breast cancer including HER 2 , EGFR , MYC , CCND 1 , and MDM 2 . ^^^ To assess the prognostic importance of amplifications and coamplifications of HER 2 , EGFR , MYC , CCND 1 , and MDM 2 in breast cancer , we analyzed a breast cancer tissue microarray containing samples from 2197 cancers with follow up information . ^^^ Fluorescence in situ hybridizations revealed amplifications of CCND 1 in 20 . 1 % , HER 2 in 17 . 3 % , MDM 2 in 5 . 7 % , MYC in 5 . 3 % , and EGFR in 0 . 8 % of the tumors . ^^^ Coamplifications of one or several other oncogenes occurred in 29 . 6 % of CCND 1 , 43 % of HER 2 , 55 . 7 % of MDM 2 , 65 % of MYC , and 72 . 8 % of EGFR amplified cancers . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
While the prognostic significance of EGFR overexpression has not been well defined , overexpression of the HER 2 oncoprotein has been associated with biological aggressiveness and poor prognosis in most series . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The epidermal growth factor system has been associated to prognosis in patients with bladder cancer based mainly on the expression of the epidermal growth factor ( EGF ) receptor 1 ( EGFR ) and HER 2 and their activating ligands . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
RESULTS : In addition to HER 2 and epidermal growth factor receptor , trastuzumab down regulated Bcl 2 , but not Bcl XL , protein , and mRNA expression in BT 474 cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Prognostic significance of p 53 , Her 2 , and EGFR overexpression in borderline and epithelial ovarian cancer . ^^^ The objective of the study was to evaluate the prognostic effect of p 53 , Her 2 , and EGFR in borderline and epithelial ovarian cancer . ^^^ Tumor tissue from 85 patients with borderline and 783 patients with epithelial ovarian cancer stage 1 4 were analyzed immunohistochemically for p 53 positivity and over expression of Her 2 and EGFR . ^^^ In the ovarian cancer ( OC ) group 415 patients ( 53 % ) had p 53 positive tumors , 272 ( 35 % ) had tumors with Her 2 over expression , and 483 ( 62 % ) had over expression of EGFR . ^^^ In the borderline group Her 2 and EGFR over expression in combination , adjusted for age and p 53 , significantly improved the prognosis . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Epidermal growth factor receptor ( EGFR ) and HER 2 are associated with a poor prognosis in various cancers , including prostate cancer . ^^^ The presence of HER 2 ( Western blot ) and EGFR ( 5830 fmol / mg protein , ligand binding assay ) was assessed in the hormone refractory human prostate cancer cell line , DU 145 . ^^^ Cells were exposed to the selective EGFR TKI ( EGFR tyrosine kinase inhibitor ) gefitinib ( ' Iressa ; ZD 1839 ) and / or the HER 2 targeted monoclonal antibody trastuzumab ( ' Herceptin ' ) , for 96 h . ^^^ These results indicate an antagonistic interaction between EGFR and HER 2 targeting and provide molecular mechanisms supporting this observation . ^^^ Data from DU 145 cells suggest that dual targeting of EGFR and HER 2 may be inappropriate for the treatment of hormone refractory prostate cancer , especially in the context of their combination with RX . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We also revealed that tyrosine phosphorylation of HER 2 induced by both lysophospholipids was significantly attenuated by two inhibitors , an epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor , AG 1478 , and a broad spectrum matrix metalloproteinase inhibitor , GM 6001 . ^^^ This suggests that the pathway of HER 2 transactivation induced by these lysophospholipids is dependent on the proteolytically released EGFR ligands . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : To assess the status of EGFR , HER 2 , and CCND 1 at the gene and protein levels in esophageal squamous cell carcinoma . ^^^ METHODS : Dual color FISH assays were performed using DNA probes for EGFR / CEP 7 , HER 2 / CEP 17 , and CCND1 / CEP 11 . ^^^ Survival was not associated with EGFR or CCND 1 gene / protein status , whereas negative patients for HER 2 protein had a better survival than positive patients ( p=0 . 04 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We describe a new format of BsAb that consists of two single chain variable fragment of antibodies ( scFvs ) , one for human epidermal growth factor receptor 2 ( HER 2 ) / neu and the other for CD 16 , heterodimerized by a `` knobs into holes ' ' device from the CH 3 domains of the human IgG 1 Fc fragment . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Tissue microarray analysis of EGFR and HER 2 oncogene copy number alterations in squamous cell carcinoma of the larynx . ^^^ PURPOSE : To evaluate EGFR and HER 2 copy number changes and to assess their significance to tumor progression in a large group of patients with larynx cancer through the construction of a tissue microarray ( TMA ) consisting of 1 , 385 biopsies . ^^^ FISH was successful for EGFR in 1 , 080 ( 77 . 98 % ) and for HER 2 in 683 ( 49 . 31 % ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The high incidence of human epidermal growth factor receptor ( HER ) 2 overexpression on breast and various other cancer cells and the prognostic and potentially predictive value of HER 2 render this growth receptor a novel and important therapeutic target . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Also , treatment with 6 mug / cm ( 2 ) crocidolite for 24 h diminished the phosphorylation levels of human EGFR 2 ( HER 2 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In this study , EGFR and HER 2 gene amplification and expression were analysed by fluorescence in situ hybridization and immunohistochemistry , respectively , in a cohort of matched tumour pairs ( one taken before and one after hormone relapse ) from 49 prostate cancer patients . ^^^ No EGFR amplification and low level , heterogeneous HER 2 amplification were observed ( 6 . 5 % ) . ^^^ Almost one quarter of the cases ( 12 / 49 , 24 . 5 % ) showed increased HER 2 or EGFR expression at hormone relapse ; this was associated with a significant reduction in time from hormone relapse to death ( p = 0 . 0003 ) . ^^^ EGFR and HER 2 amplification do not play a significant role in prostate cancer , but increased expression of HER 2 or EGFR may influence progression to androgen independence in about a quarter of cases as a rise in EGFR / HER2 expression at hormone relapse is associated with a significant reduction in time to death . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The receptor tyrosine kinase HER 2 and its rat homologue neu were independently identified as close relatives of erbB , the gene encoding the epidermal growth factor receptor ( EGFR ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Prominent among the kinases dependent on Hsp 90 is the ErbB family member HER 2 , which is frequently overexpressed in adenocarcinoma and is associated with a poor prognosis and resistance to chemotherapy . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
After 4 hours of exposure , cetuximab reduced epidermal growth factor ( EGF ) induced phosphorylation of EGFR ( pEGFR ) and HER 2 ( pHER 2 ) in cetuximab sensitive cell lines but not in cetuximab resistant cell lines . ^^^ In the absence of EGF , cetuximab alone increased the level of pEGFR and pHER 2 above that seen in untreated control cells in both sensitive and resistant cell lines that were EGFR and HER 2 positive , but not in EGFR or HER 2 negative lines . ^^^ Despite the cetuximab induced increase in phosphorylation of EGFR and HER 2 , peak EGF induced levels of pEGFR and pHER 2 were reduced by cetuximab in the cetuximab sensitive lines but not in the resistant lines . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
A series of new 6 , 7 disubstituted 4 ( arylamino ) quinoline 3 carbonitrile derivatives that function as irreversible inhibitors of human epidermal growth factor receptor 2 ( HER 2 ) and epidermal growth factor receptor ( EGFR ) kinases have been prepared . ^^^ These compounds demonstrated enhanced activities for inhibiting HER 2 kinase and the growth of HER 2 positive cells compared to our EGFR kinase inhibitor 86 ( EKB 569 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Early success of combined EGFR and Her 2 receptor blockade as a clinical strategy in breast cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Further experiments to examine expression changes of the receptor tyrosine kinases EGFR , HER 2 and estrogen receptor alpha did not reveal any alterations in BG 1 ( LT ) if compared to wild type cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Downregulation of TS , DPD , ERCC 1 , GST Pi , EGFR , and HER 2 gene expression after neoadjuvant three modality treatment in patients with esophageal cancer . ^^^ Expression levels of thymidylate synthase , dihydropyrimidine dehydrogenase , excision repair cross complementing gene 1 , glutathione S transferase Pi , epidermal growth factor receptor , and HER 2 were measured in matched preradiochemotherapy endoscopic tumor biopsies and in postradiochemotherapy resection specimens . mRNA was isolated from formalin fixed , paraffin embedded , laser microdissected tumor tissues , and a quantitative fluorescent dye real time reverse transcription polymerase chain reaction system was used for gene expression measurement . ^^^ RESULTS : There was a significant reduction in the expression levels of thymidylate synthase ( p < 0 . 01 ) , dihydropyrimidine dehydrogenase ( p = 0 . 03 ) , excision repair cross complementing gene 1 ( p < 0 . 01 ) , glutathione S transferase Pi ( p = 0 . 03 ) , HER 2 ( p < 0 . 01 ) , and epidermal growth factor receptor ( p = 0 . 04 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In addition to specific anti EGFR TKIs , there are broader acting inhibitors such as dual EGFR HER 2 inhibitors and combined anti pan ErbB and antivascular endothelial growth factor receptor inhibitors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
HER 2 ( human epidermal growth factor receptor 2 ) status became an important prognostic and predictive factor in breast carcinoma clinical management . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The family of epidermal growth factor receptors including epidermal growth factor receptor 1 ( HER 1 ) and 2 ( HER 2 ) are both expressed in ovarian cancer and are the subject of ongoing research and development . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Current anti EGFR therapies , such as cetuximab ( Erbitux ) , gefitinib ( Iressa ) , or trastuzumab ( Herceptin ) , target EGFR or HER 2 but not both . ^^^ The growth of colon ( HCT 116 , Caco 2 , and HT 29 ) and breast ( MDA MB 468 and SKBR 3 ) cancer cells expressing varying levels of EGFR , HER 2 , and / or HER 4 was inhibited by recombinant ERRP in a dose dependent manner . ^^^ Transforming growth factor alpha or heparin binding epidermal growth factor induced activation of EGFR and HER 2 was inhibited by ERRP in colon and breast cancer cells expressing high levels of EGFR or HER 2 . ^^^ In contrast , cetuximab inhibited the growth and ligand induced activation of EGFR in cell lines expressing high levels of EGFR , whereas trastuzumab was effective only in HER 2 overexpressing cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The expressions of different epidermal growth factor receptors such as EGFR ( HER 1 ) , HER 2 , HER 3 , and HER 4 have not yet been examined in these tumors . ^^^ Twenty three cases of endometrial sarcomas consisting of 20 low grade endometrial stromal sarcomas and 3 undifferentiated endometrial sarcomas were examined immunohistochemically for EGFR ( HER 1 ) , HER 2 , HER 3 , and HER 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Lastly , members of the EGFR family , particularly the HER 2 receptor , have also been recognized as crucial elements of aberrant signal transduction pathways , which induce activation of downstream signaling , involved in cellular proliferation , cell survival , and angiogenesis . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The human epidermal growth factor receptor ( Her ) family of receptor tyrosine kinases includes Her 1 , Her 2 , and Her 3 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
It is a semi quantitative immunohistochemical assay used to determine overexpression of HER 2 protein ( human epidermal growth factor receptor ) in breast cancer tissue . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : This phase 2 study investigated the efficacy , safety , and pharmacokinetics of trastuzumab monotherapy given as first line treatment once every 3 weeks ( 3 weekly ) in women with human epidermal growth factor receptor 2 ( HER 2 ) positive metastatic breast cancer ( MBC ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Tissue microarrays were analyzed by fluorescence in situ hybridization for HER 2 , CCND 1 , MYC , and EGFR amplification . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Expression of EGFR , HER 2 , HER 3 , and HER 4 in metastatic squamous cell carcinomas of the oral cavity and base of tongue . ^^^ HER 2 was not expressed to the same extent as EGFR . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : ( ) Epigallocatechin gallate ( EGCG ) inhibits activation of the epidermal growth factor receptor ( EGFR ) and human epidermal growth factor receptor 2 ( HER 2 ) and multiple downstream signaling pathways in cancer cell lines . ^^^ The EGFR and HER 2 proteins were overexpressed and constitutively activated in all of the colon cancer cell lines when compared with the FHC cell line . ^^^ Both EGCG and Poly E caused a decrease in the phosphorylated forms of EGFR and HER 2 proteins , and subsequently caused a decrease in the phosphorylated forms of the extracellular signal regulated kinase and Akt proteins . ^^^ Furthermore , when treatment was prolonged for 96 hours , 1 microg / mL of EGCG or Poly E was sufficient to inhibit growth , reduce activation of EGFR and HER 2 , and induce apoptosis . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We used two independent methods , expression of intracellular single chain antibody against HER 2 and treatment with a novel dual EGFR / HER 2 kinase inhibitor GW 572016 ( lapatinib ) . ^^^ GW 572016 was more potent in its ability to inhibit PSA expression and AR recruitment and histone acetylation than the EGFR selective kinase inhibitor ZD 1839 ( gefitinib ) , consistent with the HER 2 kinase playing the major role in AR regulation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Exposure of 11 , 11 ' dideoxy verticillin for 1 h to EGFR overexpressed MDA MB 468 human breast carcinoma cells and HER 2 overexpressed SK OV 3 human ovarian adenocarcinoma cells resulted in obvious inhibition of EGF induced phosphorylation of EGFR and HER 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunohistochemical analysis of EGFR and HER 2 in patients with metastatic squamous cell carcinoma of the skin . ^^^ Few data are available about the expression of EGFR and HER 2 in SCC of the skin . ^^^ Overexpression of EGFR and of HER 2 proteins has been reported . ^^^ The purpose of this study was to investigate the expression of EGFR and HER 2 in a series of metastatic SCC of the skin . ^^^ PATIENTS AND METHODS : EGFR and HER 2 expression was studied by immunochemistry on 13 specimens of metastatic recurrence and on 2 primary lesions of these tumours . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
EGFR and Her 2 regulate the constitutive activation of NF kappaB in PC 3 prostate cancer cells . ^^^ METHODS AND RESULTS : EGFR , Her 2 , and ErbB 3 are expressed and constitutively activated in PC 3 , DU 145 , and LNCaP prostate cancer cells lines . ^^^ Using several pharmacological ErbB inhibitors , we demonstrate that EGFR and Her 2 are involved in the constitutive activation of NF kappaB in PC 3 cells through two different mechanisms . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Endogenous RPTPkappa associated with EGF receptor and HER 2 , resulting in suppression of basal and ErbB ligand induced proliferation and receptor phosphorylation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We show that nanoshell bioconjugates can be used to effectively target and image human epidermal growth factor receptor 2 ( HER 2 ) , a clinically relevant biomarker , in live human breast carcinoma cells . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
To investigate the role of nanoscale rafts in EGFR dynamics , we used single molecule fluorescence imaging to track individual receptors and their dimerization partner , human epidermal growth factor receptor 2 ( HER 2 ) , in the membrane of human mammary epithelial cells . ^^^ EGFR was significantly less mobile than HER 2 . ^^^ This difference was likely due to F actin because its depolymerization led to similar diffusion patterns between the EGFR and HER 2 . ^^^ Our observations suggest that membrane cholesterol provides a dynamic environment that facilitates the free motion of EGFR and HER 2 , possibly by modulating the dynamic state of F actin . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : This randomized , multicenter trial compared first line trastuzumab plus docetaxel versus docetaxel alone in patients with human epidermal growth factor receptor 2 ( HER 2 ) positive metastatic breast cancer ( MBC ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : Erb 1 ( epidermal growth factor receptor , EGFR ) and Erb 2 ( Her 2 ) are two of the best characterized members in the EGFR pathway . ^^^ Our objective in this study was to investigate the clinical relevance of EGFR and Her 2 expression in bladder cancer cases from four prospective Radiation Therapy Oncology Group ( RTOG ) bladder preservation trials using cisplatin containing chemoradiation ( RTOG 8802 , 8903 , 9506 , and 9706 ) . ^^^ METHODS AND MATERIALS : Tumors from 73 cases from patients with muscle invading T 2 T4a bladder cancers had slides interpretable for EGFR staining ; 55 cases had slides interpretable for Her 2 staining . ^^^ Expression of the epidermal growth factor receptor and Her 2 are predictors of favorable outcome and reduced complete response rates , respectively , in patients with muscle invading bladder cancers treated by concurrent radiation and cisplatin based chemotherapy : a report from the Radiation Therapy Oncology Group . ^^^ CONCLUSION : Epidermal growth factor receptor expression appears to correlate significantly with improved outcome in bladder cancer , whereas Her 2 expression is significantly associated only with reduced CR rates after chemoradiation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We observed no mutations in exons 18 , 19 , and 21 of EGFR gene in LK 2 , LK2 / mock and two HER 2 trasfectants when we observed in frame deletion mutations ( E 746 A750 ) adjacent to K 745 in a gefitinib sensitive NSCLC cell line , PC 9 . ^^^ This study is the first to show that under basal growth conditions , HER 2 sensitizes low EGFR NSCLC cell lines to growth inhibition by gefitinib . . ^^^ HER 2 overexpression increases sensitivity to gefitinib , an epidermal growth factor receptor tyrosine kinase inhibitor , through inhibition of HER2 / HER3 heterodimer formation in lung cancer cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The diverse signaling network of EGFR , HER 2 , HER 3 and HER 4 tyrosine kinase receptors and the consequences for therapeutic approaches . ^^^ There are clinical indications supporting the concept that none of the receptors : EGFR , HER 2 , HER 3 and HER 4 can be considered as the stand alone receptor in breast cancer development and clinical course of the disease . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Recently , it has been reported that epidermal growth factor receptor [ corrected ] ( EGFR ) and / or human epidermal growth factor receptor [ corrected ] 2 ( HER 2 ) expressions are associated with LN 5 and / or COX 2 expressions in a few carcinoma cell lines and human tumor tissue . ^^^ LN 5 , COX 2 , EGFR , and HER 2 expressions were examined immunohistochemically in 67 patients with urothelial carcinomas ( UCs ) , and associations among these 4 biomarkers and clinicopathologic characteristics were investigated . ^^^ Overexpression of LN 5 , COX 2 , EGFR , and HER 2 was observed in 16 ( 23 . 9 % ) , 34 ( 50 . 7 % ) , 42 ( 62 . 7 % ) , and 15 ( 22 . 4 % ) of 67 patients , respectively . ^^^ Concerning EGFR and HER 2 , high grade ( EGFR , P = . 0009 ; HER 2 , P = . 003 ) and nonpapillary ( EGFR , P = . 016 ; HER 2 , P = . 0002 ) UCs had a significantly higher overexpression rate . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Other biological prognostic factors such as EGFR , HER 2 , glutathione S transferase ( GST ) and MDR were evaluated in 50 cases . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
However , most important biomarkers in a clinical setting are ER ( estrogen receptors ) and HER 2 ( human epidermal growth factor receptor 2 ) , but still only as predictive markers for tamoxifen and trastuzumab therapy . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We studied the association of gefitinib with trastuzumab on the androgen refractory prostate cancer cell line DU 145 expressing both epidermal growth factor receptor ( EGFR ) and HER 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
EGFR gene amplification in breast cancer : correlation with epidermal growth factor receptor mRNA and protein expression and HER 2 status and absence of EGFR activating mutations . ^^^ EGFR gene amplification in breast cancer : correlation with epidermal growth factor receptor mRNA and protein expression and HER 2 status and absence of EGFR activating mutations . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The 21 samples studied universally and strongly expressed EGFR and were negative for HER 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Most BRCA 1 carcinomas have the basal cell phenotype , a subtype of high grade , highly proliferating , estrogen receptor and HER 2 negative breast carcinomas , characterized by the expression of basal or myoepithelial markers such as basal keratins , P cadherin , epidermal growth factor receptor , etc . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Among them , epidermal growth factor receptor and Her 2 have been effectively targeted by monoclonal antibodies . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Comparisons were also made of clinical response with ultrasound response , actual and feasible surgery with feasible surgery at baseline , OR in human epidermal growth factor receptor 2 ( HER 2 ) positive cancers , and tolerability . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunohistochemistry using epidermal growth factor receptor , HER 2 , HER 3 , HER 4 , and PR antibodies was done . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We previously demonstrated that primary osteosarcoma cells express cell surface EGFR and Her 2 , with the p 80 isoform of Her 4 localized to the nucleus . ^^^ PROCEDURES : We cultured early passage osteosarcoma cell lines in the presence or absence of the pan erbB inhibitor CI 1033 and examined the phosphorylation status of EGFR , Her 2 , and Her 4 by immunohistochemistry , cell based ELISA , flow cytometry and two dimensional Western blot . ^^^ RESULTS : EGFR , Her 2 , and Her 4 were constitutively phosphorylated in early passage osteosarcoma cells cultured in vitro . ^^^ CONCLUSIONS : EGFR , Her 2 , and Her 4 are constitutively phosphorylated in early passage osteosarcoma cells in tissue culture , and erbB signaling provides essential growth and anti apoptotic signals to osteosarcoma cells . ^^^ BACKGROUND : The role of erbB tyrosine kinases , especially Her 2 , in osteosarcoma has engendered intense debate . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Recent research suggests that women who develop breast cancer between the ages of 30 34 may have specific tumour characteristics : Those with high grade , oestrogen receptor negative , human epidermal growth factor receptor 2 ( HER 2 ) negative tumours have between a 10 % and 27 % chance of being a BRCA 1 gene carrier . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : In a previous gene expression array study , we identified some 300 genes that were differentially expressed in human epidermal growth factor receptor tyrosine kinase 2 ( HER 2 ) positive versus HER 2 negative breast cancer cells . ^^^ The relationship between the expression of all six membrane proteins and a variety of pathologic and biological variables , including estrogen receptor , HER 2 , and epidermal growth factor receptor status , was also examined . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Metaplastic breast carcinomas are negative for Her 2 but frequently express EGFR ( Her 1 ) : potential relevance to adjuvant treatment with EGFR tyrosine kinase inhibitors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Prolonged endocrine therapy can be associated with an acquired increase in peptide growth factor signaling ( EGFR , HER 2 ) , together with cross talk activation of ER dependent gene transcription and cell growth that leads to endocrine resistance . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We previously reported that in the HT 29 human colon cancer cell line EGCG , the major biologically active component of green tea , inhibits activation of the RTKs EGFR , HER 2 , and HER 3 , and that this is associated with inhibition of multiple downstream signaling pathways . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Independent role of phosphoinositol 3 kinase ( PI3K ) and casein kinase 2 ( CK 2 ) in EGFR and Her 2 mediated constitutive NF kappaB activation in prostate cancer cells . ^^^ BACKGROUND : Recent research has highlighted the potential role of EGFR and Her 2 in the constitutive activation of NF kappaB ( NF kappaB ) in prostate cancer cells , although the mechanism by which these receptors activate NF kappaB in these cells remains unclear . ^^^ METHODS AND RESULTS : Using pharmacological and genetic approaches we show that in PC 3 cells , EGFR and Her 2 are involved in the constitutive activation of NF kappaB through two different mechanisms . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We therefore explored the association between adjuvant tamoxifen treatment in breast cancer and expression of VEGF A and VEGFR 2 , as well as human epidermal growth factor receptor 2 ( HER 2 ) , which represents a candidate gene product involved in tamoxifen resistance . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Treatment with these analogs reduced the binding capacity of EGFR by 18 64 % , and inhibited the mRNA expression for EGFR , HER 2 and 3 by 27 75 . 4 , 17 26 . 3 , and 13 . 8 46 . 6 % , respectively . ^^^ The antagonists also decreased the protein levels for EGFR by 21 34 % , HER 2 by 36 68 % and HER 3 by 43 49 % . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The progressive tumors FG P , and some tumors of SG P subgroup , presented significantly high levels of HER 1 , epidermal growth factor receptor type 2 ( HER 2 ) , TS , uPA , TP , tumor necrosis factor superfamily member 6 ( FAS ) and peptidylglycine alpha amidating mono oxygenase ( PAM ) mRNA all of which correlated with androgen receptor ( AR ) mRNA . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Amongst these , the tumorigenic roles of the Epidermal Growth Factor receptor ( EGFR ) and HER 2 have been most extensively studied . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Preclinical data indicate that HER 2 , a member of the EGFR family , could enhance TKI sensitivity . ^^^ PATIENTS AND METHODS : HER 2 gene copy numbers per cell were evaluated by fluorescent in situ hybridization ( FISH ) in 102 NSCLC patients treated with gefitinib , and previously evaluated for EGFR status by FISH , immunohistochemistry , and presence of mutations . ^^^ Patients with HER 2 FISH positive tumors displaying increased expression of EGFR protein , gene gain , or mutations ( EGFR positive ) had a significantly better OR , DCR , TTP , and OS than patients negative for both receptors . ^^^ CONCLUSION : Increased copy number of the HER 2 gene is associated with gefitinib sensitivity in EGFR positive patients , supporting use of HER 2 FISH analysis for selection of patients for TKI therapy . . ^^^ Increased HER 2 gene copy number is associated with response to gefitinib therapy in epidermal growth factor receptor positive non small cell lung cancer patients . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
It has also been reported that tamoxifen may be less effective in tumors that overexpress either HER 2 or HER 1 ( epidermal growth factor receptor ) and that signaling through these receptors reduces PR expression in experimental models . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Included in this group are receptor tyrosine kinases such as epidermal growth factor receptor , insulin like growth factor receptor 1 , fibroblast growth factor receptor 3 , KIT , and HER 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In addition , 1 , 25D decreased tyrosine phosphorylation of HER 2 , an EGFR family member inactivated by PAcP , and the HER 2 downstream adaptor protein p 52 Shc in C 81 LN cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
New dual inhibitors of EGFR and HER 2 protein tyrosine kinases . ^^^ A novel series of dual EGFR and HER 2 inhibitors based on the pyrrolo [ 2 , 1 f ] [ 1 , 2 , 4 ] triazine nucleus is described . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Studies of cell models and profiling of clinical breast cancer material to reveal the mechanisms of resistance to anti oestrogen therapy , and to tamoxifen in particular , have reported that this phenomenon can be associated with increased expression and signalling through erbB Type 1 growth factor receptors , notably the epidermal growth factor receptor ( EGFR ) and HER 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
This paper presents our immunohistochemical evidence that EGFR / HER2 signalling ( i . e . transforming growth factor ( TGF ) alpha , EGFR and HER 2 expression ; phosphorylation of EGFR , HER 2 and ERK1 / 2 MAP kinase ) is also prominent in clinical de novo resistant and modestly increased in acquired tamoxifen resistant states , suggesting that anti EGFR / HER2 strategies may prove valuable treatments . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Because overexpression of the human epidermal growth factor receptor 2 ( HER 2 ) was found in the specimen from her right axillary lymph node , she was treated with trastuzumab and vinorelbine . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
EGFR high dosage amplification , like in HER 2 , was not demonstrated . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Epidermal growth factor receptor ( EGFR ) and HER2 / neu ( HER 2 ) tyrosine kinases have been implicated in the development and progression of several human cancers and are targets for therapeutic intervention . ^^^ The aim of this study was to evaluate for HER 2 and EGFR expression in cases of endometrial carcinosarcoma . ^^^ METHODS : Formalin fixed , paraffin embedded sections from 55 cases of confirmed endometrial carcinosarcoma were immunostained with commercially available antibodies to EGFR and HER 2 . ^^^ HER 2 gene amplification and EGFR expression were correlated with several prognostic variables . ^^^ EGFR expression and HER 2 gene amplification did not show significant correlation with disease progression , disease free survival or overall survival . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Epidermal growth factor receptor 1 ( EGFR ) and EGFR 2 ( HER 2 ) have become major targets for cancer treatment . ^^^ Thus , a better knowledge on the signaling pathways activated by EGFR and HER 2 may help unravel novel therapeutic targets and molecular markers of response . ^^^ Here , we show that treatment of breast cancer cell lines with blocking antibodies against EGFR ( cetuximab ) or HER 2 ( trastuzumab ) promotes the specific induction of proapoptotic Bnip3L and chemosensitization . ^^^ Therefore , blockading EGFR or HER 2 specifically up regulates Bnip3L , which is required for chemosensitization of breast cancer cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : To critically assess the accuracy and reproducibility of human epidermal growth factor receptor type 2 ( HER 2 ) testing in outside / local community based hospitals versus two centralized reference laboratories and its effect on selection of women for trastuzumab ( Herceptin ) based clinical trials . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : The objective of this study was to determine whether the addition of trastuzumab to chemotherapy in the neoadjuvant setting could increase pathologic complete response ( pCR ) rate in patients with human epidermal growth factor receptor 2 ( HER 2 ) positive disease . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : To retrospectively identify radiographic characteristics of stage 1 non small cell lung cancer ( NSCLC ) that may correlate with epidermal growth factor receptor ( EGFR ) or HER 2 expression or with prognosis . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
A subset of high grade pulmonary neuroendocrine carcinomas shows up regulation of matrix metalloproteinase 7 associated with nuclear beta catenin immunoreactivity , independent of EGFR and HER 2 gene amplification or expression . ^^^ Less is known on beta catenin transactivation in high grade pulmonary neuroendocrine tumors and on the status of beta catenin activating EGFR and human epidermal growth factor receptor 2 ( HER 2 ) or beta catenin target genes cyclin D 1 and matrix metalloproteinase 7 ( MMP 7 ) . beta catenin immunoreactivity was evaluated in 51 large cell neuroendocrine carcinomas ( LCNEC ) and 45 small cell lung carcinomas ( SCLC ) . ^^^ Nineteen cases were assessed for beta catenin gene exon 3 mutations , expression of MMP 7 , and expression / gene amplification of EGFR , HER 2 , and cyclin D 1 . beta catenin was expressed in all 96 high grade neuroendocrine tumors , the vast majority ( 94 % ) showing > 50 % immunopositive cells . ^^^ In LCNEC , but not in SCLC , the disarrayed patterns correlated with EGFR and HER 2 protein expression . beta catenin nuclear accumulation was found in nine tumors , including seven LCNEC and two SCLC , and was always associated with disarrayed immunoreactivity and increased MMP 7 , but not cyclin D 1 expression . ^^^ These cases , however , did not show beta catenin gene mutations or EGFR and HER 2 gene amplification or expression . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Asp 746 to glycine change may have a greater influence than Cys 751 to serine change in accounting for ligand selectivity between EGFR and HER 2 at the ATP site . ^^^ We have carried out up to 8 . 0 ns molecular dynamics simulation on the ATP bound complexes of EGFR and HER 2 ( homology model ) receptor kinase domains to explore the possible consequences of amino acid residue changes in or close to the ATP site that might provide insights for selectivity of these kinases towards ATP site inhibitors . ^^^ The movement of Arg 784 in HER 2 appears to result from the absence of an anchoring residue like Asp 746 in EGFR , which has been changed to Gly 778 in HER 2 . ^^^ This might be an important contributory factor to differences in selectivity of the ligands between the two kinases , probably more so than the conservative change of Cys 751 of EGFR to serine in HER 2 at the ATP site . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Gene amplification and protein expression of EGFR and HER 2 by chromogenic in situ hybridisation and immunohistochemistry in atypical adenomatous hyperplasia and adenocarcinoma of the lung . ^^^ AIMS : To investigate the importance of gene amplification and EGFR ( epidermal growth factor receptor ) and HER 2 protein expression during the progression of adenocarcinoma of the lung . ^^^ METHODS : EGFR and HER 2 gene amplification was examined in atypical adenomatous hyperplasia ( AAH ) , bronchioloalveolar carcinoma ( BAC ) , and adenocarcinoma with mixed subtypes ( MX ) by chromogenic in situ hybridisation ( CISH ) , and protein expression was examined by immunohistochemistry using paraffin wax embedded tissues . ^^^ RESULTS : EGFR and HER 2 gene amplification was found in four and two of 86 cases , respectively , and was detected only in the invasive components of MX . ^^^ EGFR and HER 2 protein expression was seen in 24 and 18 of 86 cases , respectively . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
To date , the only widely accepted markers for routine use in breast cancer are the oestrogen receptor ( ER ) , progesterone receptor ( PR ) and human epidermal growth factor receptor , HER 2 ( c erbB2 / neu ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The MCF 10HER 2E7 and HER 2 / E6E7 cells exhibited constitutive activation of a form of epidermal growth factor receptor ( EGFR ) that had a faster electrophoretic mobility than EGFR activated by exogenous growth factors . ^^^ Exposure of cells with EGFR activation to ZD 1839 ( Iressa ) , at concentrations specific for EGFR , had little or no influence on proliferation of cells with amplified HER 2 but little or no EGFR . ^^^ These results indicate that HER 2 , E 6 , and E 7 cooperate with endogenous EGFR to yield fully transformed cells . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Tumor examination has identified a growth factor receptor gene , human epidermal growth factor receptor ( HER 2 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The molecular mechanisms for frequent epidermal growth factor receptor ( EGFR , a tyrosine kinase [ TK ] ) and HER 2 ( the preferred coreceptor of EGFR ) overexpression in lung cancer are poorly understood . ^^^ Recent studies have shown the mutations of the TK domain in EGFR and HER 2 to be present in lung cancer . ^^^ The purpose of this study was to investigate the relationship between mutation status and expression of EGFR and HER 2 in lung cancer . ^^^ Immunostaining took place for EGFR and HER 2 , and mutational analyses for EGFR , HER 2 , and KRAS ( a signaling protein ) were conducted using 130 resected lung cancer specimens . ^^^ Thirty seven EGFR mutations ( 28 % ) and 8 HER 2 mutations ( 6 % ) , both of the TK domains , and 5 KRAS ( 4 % ) mutations were found , whereas 73 ( 56 % ) EGFR and 47 ( 36 % ) HER 2 overexpressions were found . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
While mutational status is of great importance in determining response to TKIs , it is not the sole factor , and evidence is accumulating that EGFR gene amplification , other members of the EGFR family ( HER 2 , HER 3 ) and genes downstream of EGFR signaling ( KRAS , BRAF ) , may be involved in cancer pathogenesis and the response of TKIs . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The dependence on gene copy number or expression levels of HER 2 and epidermal growth factor receptor ( EGFR ) for therapeutic efficacy of trastuzumab and cetuximab ( Erbitux ) , respectively , supports the importance of selecting suitable patient populations based on their pharmacogenetic profile . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Furthermore , preclinical studies indicate that combining fulvestrant with growth factor targeted agents , such as the epidermal growth factor receptor ( EGFR / HER1 ) tyrosine kinase inhibitor gefitinib ( IRESSA ) or the anti human HER 2 monoclonal antibody trastuzumab ( ' Herceptin ' ) , may result in greater anti tumor activity than either agent alone . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
An important recent advance in anticancer therapy was the development of molecular targeting drugs , such as the epidermal growth factor receptor ( EGFR ) targeting drug ZD 1839 ( Iressa ) and the HER 2 trageting anti HER 2 monoclonal antibody trastuzumab ( Herceptin ) . ^^^ NSCLC cells often express both EGFR and HER 2 . ^^^ In culture ZD 1839 inhibited the growth of four NSCLC cell lines ( A 549 , NCI H 23 , NCI H 727 , and NCI H 661 ) that expressed various levels of EGFR , HER 2 , HER 3 , and HER 4 . ^^^ The combination treatment significantly inhibited the phosphorylation of EGFR , HER 2 , retinoblastoma , extracellular signal regulated kinase 1 / 2 , and protein kinase B / Akt in A 549 cells , but not in NCI H 23 cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : Trastuzumab is effective in treating human epidermal growth factor receptor 2 ( HER 2 ) positive breast cancer , but it increases frequency of cardiac dysfunction ( CD ) when used with or after anthracyclines . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
HER 2 is a ligand less member of the HER family that functions as the preferred coreceptor for epidermal growth factor receptor ( EGFR ) , HER 3 , and HER 4 . ^^^ RESULTS : HER 2 was robustly expressed in all eight ovarian carcinoma cell lines ; expression of EGFR and HER 3 was variable . ^^^ BACKGROUND : Human epidermal growth factor receptor 2 ( HER 2 ) is overexpressed in 25 30 % of ovarian carcinoma cases and a correlation between increased HER 2 expression and decreased survival has been demonstrated . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Well known predictors for response to systemic therapy include estrogen receptor status HER 2 status , c kit mutation , and epidermal growth factor receptor mutation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
No tumors showed a mutation of EGFR , KRAS , and HER 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Metaplastic breast carcinomas exhibit EGFR , but not HER 2 , gene amplification and overexpression : immunohistochemical and chromogenic in situ hybridization analysis . ^^^ Human epidermal growth factor receptor ( HER ) 2 and EGFR have attracted much attention in the medical literature over the past few years owing to the fact that humanized monoclonal antibodies against HER 2 and therapies directed against the extracellular ligand binding domain or the intracellular tyrosine kinase domain of EGFR have proven successful in treating certain types of human cancer . ^^^ We investigated whether HER 2 and EGFR overexpression was present and evaluated gene amplification in a series of metaplastic breast carcinomas . ^^^ METHOD : Twenty five metaplastic breast carcinomas were immunohistochemically analyzed using a monoclonal antibody ( 31G7 ) for EGFR and two antibodies for HER 2 ( Herceptest and CB 11 ) and scored using the Herceptest scoring system . ^^^ Gene amplification was evaluated by chromogenic in situ hybridization using Zymed Spot Light EGFR and HER 2 amplification probe . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Expression of KIT , EGFR , HER 2 and tyrosine phosphorylation in undifferentiated thyroid carcinoma : implication for a new therapeutic approach . ^^^ The KIT , epidermal growth factor receptor ( EGFR ) and HER 2 oncoproteins have tyrosine kinase activity and are molecular targets in human cancer therapy . ^^^ To clarify the significance of KIT , EGFR , and HER 2 in undifferentiated thyroid carcinoma ( UTC ) , the expression of these receptors and tyrosine phosphorylation was examined immunohistochemically in resected cases of UTC and papillary thyroid carcinoma ( PTC ) . ^^^ KIT , EGFR , and HER 2 were also examined at the protein and mRNA levels in five UTC cell lines . ^^^ KIT expression ( 1+ ) , EGFR overexpression ( 2+ / 3+ ) , HER 2 expression ( 1+ ) , and tyrosine phosphorylation were detected immunohistochemically in 40 % , 70 % , 10 % , and 50 % of the 10 UTC . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
A total of 82 NSCLC patients treated with gefitinib ( 250 mg ) , and previously evaluated for EGFR and HER 2 status by fluorescence in situ hybridisation ( FISH ) and DNA sequencing , and for Phospho Akt status by immunohistochemistry , were investigated for HER 3 genomic gain by FISH . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Skin toxicity , a common drug related adverse event observed in cancer patients treated with epidermal growth factor receptor ( EGFR ) directed therapies is rarely seen with therapies targeting HER 2 . ^^^ This study reports the significance of the EGFR and HER 2 dimerization status in skin with regard to these dermatologic side effects . ^^^ We demonstrate the differential effect of HER directed therapies on the ligand driven activation status of EGFR , HER 2 and MAPK in normal human epidermal keratinocytes . ^^^ The presence of [ p ] EGFR and [ p ] MAPK , but the absence of [ p ] HER 2 , demonstrates productive signaling via EGFR but not HER 2 in human skin . ^^^ These data illustrate the importance of the EGFR dimerization partner in human skin and suggests that inhibition of EGFR homodimer signaling rather than EGFR / HER2 heterodimer signaling maybe the key molecular event determining dermatologic toxicity discrepancies observed between EGFR targeted versus HER 2 targeted therapies . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The human epidermal growth factor receptor 2 ( HER 2 ) protein , a transmembrane growth factor receptor , is frequently overexpressed in malignancies , causing activation of the phosphatidylinositol 3 kinase ( PI3K ) and extracellular signal regulated kinase ( ERK ) signal pathways . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
New sections , with core and surgical specimens on the same slides , were stained for estrogen receptor ( ER ) , progesterone receptor ( PR ) , and human epidermal growth factor receptor 2 ( HER 2 ) immunohistochemistry ( IHC ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The expression of epidermal growth factor receptor ( EGFR ) family , human epidermal growth factor receptor 2 ( HER 2 ) and EGFR , was also examined in 53 cases , and consequently , it was indicated that survivin positivity might be correlated with the coexpression of HER 2 and EGFR . ^^^ To clarify the regulatory mechanism of survivin expression in breast cancer cells , the effect of HER 2 and / or EGFR expression on the survivin levels was examined . ^^^ It was revealed that the survivin protein level was up regulated by the coexpression of HER 2 and EGFR , leading to the increased resistance against etoposide induced apoptosis in breast cancer cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The majority of breast cancer patients who achieve an initial therapeutic response to the human epidermal growth factor receptor 2 ( HER 2 ) targeted antibody trastuzumab will show disease progression within 1 year . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunohistochemistry for estrogen receptor ( ER ) , HER 2 , EGFR , smooth muscle actin ( SMA ) , p 63 , CD 10 , cytokeratin 5 / 6 , cytokeratin 8 / 18 , and vimentin was performed on 18 basal like , 16 luminal , and 12 HER2+ tumors . ^^^ The most consistent immunophenotype seen in the basal like tumors was negativity for ER and HER 2 , and positivity for vimentin , EGFR , cytokeratin 8 / 18 , and cytokeratin 5 / 6 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
MATERIALS AND METHODS : Previously treated patients with human epidermal growth factor receptor 2 ( HER 2 ) overexpressing MBC were enrolled in a multicentre phase 2 study ( DAKO Hercep Test 3+ ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Caveolin 1 is down regulated and inversely correlated with HER 2 and EGFR expression status in invasive ductal carcinoma of the breast . ^^^ Using a tissue microarray , caveolin 1 expression was also correlated with the expression of other antigens such as eostrogen receptor , progesterone receptor , epidermal growth factor receptor ( EGFR ) , HER 2 , beta catenin , E cadherin , p 53 , Ki 67 and with clinicopathological parameters . ^^^ Furthermore , a statistically significant inverse correlation between caveolin 1 and EGFR and HER 2 was noted ( P < 0 . 001 ) . ^^^ Caveolin 1 also shows an inverse correlation with EGFR and HER 2 , which fits with its function as a negative regulator of signal transduction . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
METHODS : The immunohistochemical expression of EGFR ( Her 1 ) , Her 2 , Her 3 , and Her 4 was analyzed in a group of ovarian GCTs encompassing 38 adult type and 2 juvenile type . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We have analyzed a breast cancer TMA containing 2 , 517 breast tissues , including 2 , 222 neoplastic and 295 normal or premalignant samples , for Ki 67 labeling index ( Ki 67 LI ) and additional markers with a known relationship to Ki 67 LI by immunohistochemistry ( ER , PR , Bcl 2 , Egfr , p 16 , p 53 ) and Fluorescence in situ hybridization ( HER 2 , MDM 2 , CCND 1 , MYC ) . ^^^ A high Ki 67 LI was linked to tumor phenotype including grade ( p < 0 . 0001 ) , stage ( p < 0 . 0001 ) , nodal stage ( p = 0 . 0018 ) , and patient prognosis ( p < 0 . 0001 ) , elevated protein levels of p 53 , p 16 and Egfr , reduced levels of Bcl 2 , ER , and PR ( p < 0 . 0001 each ) , as well as amplifications of HER 2 , MYC , CCND 1 and MDM 2 ( p < 0 . 0001 each ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
BACKGROUND : Trastuzumab plus chemotherapy has become the standard of care for women with human epidermal growth factor receptor 2 ( HER 2 ) positive metastatic breast cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Expression of BRCA 1 , HER 1 ( EGFR ) and HER 2 in sporadic breast cancer and relationships to other clinicopathological prognostic features . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The problems that have been encountered and have delayed the development of other diagnostic tools are exemplified in the development of tests for human epidermal growth factor receptor ( HER 2 ) overexpression , for predictors of response to epidermal growth factor receptor inhibitors , and for the detection of residual disease following chemotherapy . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Consistent with this hypothesis , several recent clinical studies have found that ER+ / PR breast cancers overexpress human epidermal growth factor receptor ( HER ) 1 and HER 2 compared with ER+ / PR+ breast cancers . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We studied epithelial expression of EGF , transforming growth factor a , amphiregulin , heregulin ( HRG ) , betacellulin ( BTC ) , and their receptors , EGFR , HER 2 , and HER 3 , by immunohistochemical analysis in resected bronchial tissue from 20 subjects with ( forced expiratory volume in 1 second [ FEV ( 1 ) ] < 75 % of predicted value ) and 18 without ( FEV ( 1 ) > 85 % predicted value ) COPD . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Although clinically effective monoclonal antibodies ( MAbs ) have been developed to target HER 2 and EGFR , the remaining two family members , HER 3 and HER 4 , have not been the subject of significant efforts . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We previously reported that in HT 29 human colon cancer cells EGCG , the major biologically active component of green tea , inhibits activation of two members of this family , EGFR and HER 2 , and multiple downstream signaling pathways . ^^^ Treatment of these cells with 20 microg / ml of EGCG ( the IC 50 concentration for growth inhibition ) caused , within 6 hours , a decrease in the phosphorylated ( i . e . activated ) forms of not only EGFR and HER 2 , but also HER 3 . ^^^ With a longer incubation time , 96 hours , a very low dose ( 1 . 0 microg / ml ) of EGCG also caused inhibition of cell growth , inhibition of activation of EGFR , HER 2 , and HER 3 , a decrease in the levels of COX 2 and Bcl xL proteins , and apoptosis . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Investigation of about 60 loci containing genes associated with the epidermal growth factor family ( epidermal growth factor receptor , HER 2 , HER 3 and HER 4 ) revealed that all seven cell lines harbor copy number changes to multiple genes in these pathways . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In the current study , we examined the effects of recombinant ERRP on the growth and ligand induced activation of multiple members of erbB family in three pancreatic cancer cell lines that express varying levels of EGFR and other member ( s ) of its family , specifically HER 2 . ^^^ ERRP also inhibited ligand induced activation of EGFR , HER 2 , and HER 3 ( ErbB 3 ) . ^^^ In contrast , Erbitux and Herceptin only partially or modestly inhibited activation of EGFR , HER 2 , and HER 3 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Lapatinib ( GW 572016 ) is a selective inhibitor of both epidermal growth factor receptor ( EGFR ) and HER 2 tyrosine kinases . ^^^ We further characterize its activity in combination with trastuzumab and analyze whether EGFR and HER 2 expression or changes induced in the activation of EGFR , HER 2 , Raf , AKT , or extracellular signal regulated kinase ( ERK ) are markers of drug activity . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
AIMS AND BACKGROUND : The HER 2 gene encodes a 185 kd transmembrane glycoprotein receptor ( p 185 ( HER 2 ) ) that has partial homology with the epidermal growth factor receptor and shares intrinsic tyrosine kinase activity . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PATIENTS AND METHODS : EGFR and HER 2 gene copy numbers were assessed by fluorescence in situ hybridization ( FISH ) in 81 patients treated with gefitinib 500 mg / d ( Southwest Oncology Group protocol S 0126 ) and were correlated to treatment outcome . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Predictive markers of response like the estrogen receptor ( ER ) and the human epidermal growth factor receptor 2 ( HER 2 ) help identify those most likely to derive a survival benefit from adjuvant therapy with anti estrogens and trastuzumab therapy , respectively . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Recently , trastuzumab has had a dramatic impact on the evolution of human epidermal growth factor receptor 2 ( HER 2 ) positive early breast cancer treated with standard adjuvant modalities ; specifically , relapses , including distant relapses , have been halved . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The HER 2 oncogene encodes a transmembrane protein partially homologous to epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Their assessment for biomarkers indicative of cellular proliferation , apoptosis , and endocrine response / resistance such as estrogen and progesterone receptor status , HER 2 and epidermal growth factor receptor are considered . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunohistochemical staining for ER , progesterone receptor ( PgR ) , HER 2 and epidermal growth factor receptor ( EGFR ) was undertaken . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The efficacy of letrozole in the neoadjuvant setting further extends to those tumors with positive human epidermal growth factor receptor ( HER 1 ) and / or HER 2 expression , which are often less responsive to tamoxifen . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The prognostic role of key components of apoptotic and prosurvival pathways such as p 53 , EGFR , and HER 2 has been extensively studied because resistance to chemotherapy is often caused by failure of tumor cells to go into apoptosis . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
These lesions are estrogen receptor ( ER ) negative , progesterone receptor ( PR ) negative , and HER 2 negative ( triple negative ) , and typically express basal cytokeratins , epidermal growth factor receptor ( EGFR ) , and / or c kit . ^^^ We studied 66 cases of high nuclear grade DCIS using antibodies to ER , PR , HER 2 , three basal cytokeratins , EGFR , and c kit to determine the frequency of the triple negative phenotype , and to determine the relationship between the triple negative phenotype and expression of basal cytokeratins and other biomarkers characteristically expressed by invasive basal like carcinomas . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Our results indicate that coexpression of EGFR with HER 2 or HER 3 biases signaling to the cell surface and retards signal downregulation . ^^^ Results indicate that coexpression of EGFR with HER 2 and HER 3 at low to moderate levels may enable cells to match the response of a high HER 2 expresser . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
No relationship was observed between bortezomib effects on cell viability and expression / phosphorylation of HER 2 , epidermal growth factor receptor ( EGFR ) , AKT , or extracellular signal regulated kinase 1 / 2 ( ERK1 / 2 ) . ^^^ Molecular effects of bortezomib were further studied in SK BR 3 and BT 474 cells because they share expression of EGFR and overexpression of HER 2 while , in contrast , SK BR 3 cells were 200 fold more sensitive to this agent . ^^^ In SK BR 3 cells , a marked inhibition of EGFR , HER 2 , and AKT phosphorylation was observed at a clinically relevant concentration of bortezomib . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Detection of EGFR and HER 2 activating mutations in squamous cell carcinoma involving the head and neck . ^^^ In this report we screened 24 cases of squamous cell carcinoma , either primary in the head and neck or secondarily involving the head and neck area , for activating mutations in EGFR exons 18 , 19 , 20 , 21 , and for HER 2 exons 19 and 20 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : To evaluate the efficacy and safety of docetaxel , cisplatin , and trastuzumab as primary systemic therapy for human epidermal growth factor receptor 2 ( HER 2 ) positive , locally advanced breast cancer ( LABC ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Indeed , a number of inhibitors that target either EGFR or HER 2 , but not both , have been developed for treatment of epithelial cancers . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
For instance , the cell signaling pathways inhibited by curcumin alone include NF kappaB , AP 1 , STAT 3 , Akt , Bcl 2 , Bcl 10 ( L ) , caspases , PARP , IKK , EGFR , HER 2 , JNK , MAPK , COX 2 , and 5 LOX . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Trastuzumab ( Herceptin ) is a humanised monoclonal antibody used in the treatment of breast cancer that overexpresses human epidermal growth factor receptor 2 ( HER 2 ) , which is associated with clinically aggressive disease and a poor prognosis . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
METHODS : Mutations in the epidermal growth factor receptor gene ( EGFR ) , HER 2 , and KRAS and the methylation profile of 9 genes for NSCLC were analyzed and correlated with clinical and histologic data . ^^^ RESULTS : Thirty nine EGFR , 4 HER 2 , and 6 KRAS mutations were found in 150 NSCLC cases , with the methylation percentages of the genes ranging from 13 % to 54 % . ^^^ Mutations in EGFR , HER 2 , and KRAS were found to be present exclusively , whereas methylation tended to be present synchronously . ^^^ Exclusive mutation in epidermal growth factor receptor gene , HER 2 , and KRAS , and synchronous methylation of nonsmall cell lung cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
However , mutations of other tumor suppressor genes , including TP 53 , and protooncogenes , including KRAS , NRAS , BRAF , EGFR and HER 2 , were not found in these cell lines . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Patients and Methods : For 69 non small cell lung cancer patients treated with gefitinib , we have extended our analysis to EGFR gene copy number by fluorescence in situ hybridization , mutations in K ras , HER 2 , and exon 20 of EGFR by direct sequencing , and phosphatase and tensin homologue expression by immunohistochemistry , in addition to EGFR exons 18 , 19 , and 21 , and phosphorylations of Akt and extracellular signal regulated kinase reported previously . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The overexpression of the epidermal growth factor receptor ( EGFR ) and HER 2 underpin the growth of aggressive breast cancer ; still , it is unclear what governs the regulation of these receptors . ^^^ We reasoned that the underlying cause for growth attenuation by YB 1 ( Ser ( 102 ) ) is through the regulation of EGFR and / or HER 2 . ^^^ We determined that YB 1 ( n = 389 cases ) was positively associated with EGFR ( P < 0 . 001 , r = 0 . 213 ) , HER 2 ( P = 0 . 008 , r = 0 . 157 ) , and Ki 67 ( P < 0 . 0002 , r = 0 . 219 ) . ^^^ Overexpression of YB 1 in a breast cancer cell line increased HER 2 and EGFR . ^^^ The mutant YB 1 protein was also unable to optimally bind to the EGFR and HER 2 promoters based on chromatin immunoprecipitation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Many BRCA 1 related tumors have a distinct histological characteristics which together have been called `` basal like . ' ' Typically such tumors are ER , HER 2 and express cytokeratin 5 / 6 , cytokeratin 8 / 18 , EGFR and vimentin . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
BACKGROUND : Amplification of the human epidermal growth factor receptor type 2 ( HER 2 , also called HER2 / neu ) gene and overexpression of its product in breast cancer cells may be associated with responsiveness to anthracycline containing chemotherapy regimens . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
EXPERIMENTAL DESIGN : Immunohistochemical analysis of epidermal growth factor receptor ( EGFR ; c ErbB1 / EGFR ) , HER 2 / neu ( c ErbB2 / HER 2 ) , Ki 67 , and minichromosome maintenance protein 2 ( MCM 2 ) expression in bronchial dysplasia was undertaken to characterize molecular alterations associated with the progression of these lesions in 268 bronchoscopically obtained biopsies from 134 subjects . ^^^ RESULTS : Analysis of biopsies with the most severe diagnosis from each subject showed a linear relationship between increasing marker expression and severity of dysplastic change for EGFR ( P < 0 . 001 ) , Ki 67 ( P < 0 . 001 ) , and MCM 2 ( P = 0 . 001 ) but not HER 2 ( P = 0 . 102 ) . ^^^ Increased expression of either EGFR or HER 2 was associated with increased levels of Ki 67 and MCM 2 expression , and combined overexpression of these receptors was associated with the highest levels of proliferation , suggesting a synergistic effect . ^^^ Analysis of c ErbB1 / epidermal growth factor receptor and c ErbB2 / HER 2 expression in bronchial dysplasia : evaluation of potential targets for chemoprevention of lung cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : To investigate the impact of human epidermal growth factor receptor ( HER ) 1 and HER 2 gene amplification on endocrine therapy responsiveness , a fluorescence in situ hybridization ( FISH ) study was conducted on tumor samples from 305 postmenopausal patients with stage 2 and 3 estrogen receptor ( ER ) positive ( ER > or = 10 % ) breast cancers treated on two independent neoadjuvant endocrine therapy trials . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Human epidermal growth factor receptor 2 ( HER 2 ) overexpression has been associated with increased invasiveness in mammalian breast cancer cell lines , but the effects of overexpression on key underlying cell migration properties such as translational speed and directional persistence are not understood . ^^^ Moreover , the differential effect of HER 2 activation through heterodimerization with epidermal growth factor receptor versus human epidermal growth factor receptor 3 ( HER 3 ) on cell speed and persistence has not been studied . ^^^ Taken together , the data show that the HER 2 overexpression mediates cell migration through differential control of translational speed and directional persistence dependent on epidermal growth factor receptor HER 2 versus HER 2 HER3 heterodimerization . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Her2 / neu ( Her 2 ) is a tyrosine kinase belonging to the EGF receptor ( EGFR ) / ErbB family and is overexpressed in 20 30 % of human breast cancers . ^^^ Stably transfected cell lines overexpressing Her 2 or empty vector were generated , and the effect of an EGFR and Her 2 selective tyrosine kinase inhibitor , PD 168393 , on these cells was characterized . ^^^ Phosphoproteins that were identified included many known Her 2 signaling molecules as well as known EGFR signaling proteins that had not been previously linked to Her 2 , such as Stat 1 , Dok 1 , and delta catenin . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PATIENTS AND METHODS : Patients with human epidermal growth factor receptor 2 ( HER 2 ) positive metastatic breast cancer underwent gamma camera imaging from 15 minutes to 7 days after injection of 150 MBq 111In diethylenetriamine penta acetic acid anhydride ( DTPA ) trastuzumab , after loading dose trastuzumab , and after once a week trastuzumab doses for 11 weeks , and concomitant paclitaxel once every 3 weeks . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In this study we compared Qrt PCR results for the assessment of mRNA levels of ERa , PgR , and the members of the human epidermal growth factor receptor family , HER 1 , HER 2 , HER 3 and HER 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Activating mutations in the epidermal growth factor receptor ( EGFR ) ( 7p12 . 3 p12 . 1 ) and in the human epidermal growth factor receptor 2 ( HER 2 ) ( 17q21 . 1 ) characterize a subset of lung carcinomas . ^^^ In this study , we used high resolution melting amplicon analysis to screen for EGFR and human HER 2 activating mutations in 39 patients with primary lung adenocarcinoma . ^^^ The EGFR exons screened were exons 18 , 19 , 20 , and 21 , and the HER 2 exons screened were exons 19 and 20 . ^^^ Estrogen and progesterone receptor expression was not strong in any of the cases and did not correlate with the presence of EGFR or HER 2 mutations . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We now show that apical localization of EGFR complexes in normal fetal and ADPKD epithelia is associated with heterodimerization of EGFR ( HER 1 ) with HER 2 ( neu / ErbB2 ) , while basal membrane localization in normal adult renal epithelia is associated with EGFR ( HER 1 ) homodimers . ^^^ These studies implicate HER 2 ( neu / ErbB2 ) as an effector of apical EGFR complex mispolarization and that its inhibition should be considered a candidate for clinical therapy of ADPKD . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunohistochemical analysis of EGFR and HER 2 in patients with metastasizing melanoma , Merkel carcinoma and squamous cell carcinoma of the skin ] . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Clinicopathologic significance of EGFR and Her 2 / neu in colorectal adenocarcinomas . ^^^ METHODS : Immunohistochemistry was performed in paraffin embedded specimens of 106 colorectal carcinomas for the assessment of EGFR and Her 2 expression . ^^^ The correlation with other clinicopathologic parameters demonstrated a statistically significant expression of membranous EGFR in the older age group and a statistically significant expression of membranous Her 2 in patients with negative lymph nodes . ^^^ None of the other parameters or patient prognosis was associated with EGFR or Her 2 membranous expression . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
OBJECTIVES : To investigate the usefulness of the overexpression of the human epidermal growth factor receptor ( HER 2 ) oncoprotein in patients with bone metastatic prostate cancer as a marker for the time to recurrence and outcome after endocrine therapy . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Positive to negative change was prominent with intervening endocrine treatment , and it was significant ( p=0 . 015 ) for ER by multiple regression analysis of age , interval of sampling and from prior surgery , intervening chemotherapy , endocrine therapy and human epidermal growth factor receptor 2 ( HER 2 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
AIMS : Recently , an immunohistochemical panel comprising antibodies against HER 2 , oestrogen receptor ( ER ) , epidermal growth factor receptor ( EGFR ) and cytokeratin ( CK ) 5 / 6 was reported to identify basal like breast carcinomas , as defined by cDNA microarrays . ^^^ Immunohistochemistry with antibodies for HER 2 , ER , EGFR , CK5 / 6 , CK 14 and p 63 was performed according to standard methods . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
HER 2 kinase domain mutation results in constitutive phosphorylation and activation of HER 2 and EGFR and resistance to EGFR tyrosine kinase inhibitors . ^^^ Expression of a HER 2 mutant containing a G 776 ( YVMA ) insertion in exon 20 was more potent than wild type HER 2 in associating with and activating signal transducers , phosphorylating EGFR , and inducing survival , invasiveness , and tumorigenicity . ^^^ HER 2 ( YVMA ) transphosphorylated kinase dead EGFR ( K721R ) and EGFR ( WT ) in the presence of EGFR tyrosine kinase inhibitors ( TKIs ) . ^^^ Knockdown of mutant HER 2 in H 1781 lung cancer cells increased apoptosis and restored sensitivity to EGFR TKIs . ^^^ These data suggest that ( 1 ) HER 2 ( YVMA ) activates cellular substrates more potently than HER 2 ( WT ) ; and ( 2 ) cancer cells expressing this mutation remain sensitive to HER 2 targeted therapies but insensitive to EGFR TKIs . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Trastuzumab ( Herceptin ; Genentech ) is a recombinant humanized monoclonal antibody that targets an epitope in the extracellular domain of the human epidermal growth factor receptor 2 ( HER 2 ) protein . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Evidence is now accruing that EGFR works in concert with other ErbB family members , particularly HER 2 and ErbB 3 , to activate these signaling pathways in lung cancers . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Sensitivity to Her 2 directed therapies is complex and involves expression not only of Her 2 but also of other epidermal growth factor receptor ( EGFR ) family members , their ligands , and molecules that influence pathway activity , such as insulin like growth factor 1 receptor , PTEN , and p 27 . ^^^ The role played by Her 2 as the obligate heterodimerization partner for the other EGFR family members renders Her 2 an attractive target irrespective of receptor overexpression . ^^^ The most promising Her 2 targeted strategy will likely prove to be combinatorial approaches using an EGFR tyrosine kinase inhibitor together with Her 2 dimerization inhibitors . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In the present study , we searched for mutations of EGFR , HER 2 and KRAS in 264 resected primary NSCLC from Japanese patients and determined whether there is a correlation between genetic alterations of these genes and clinicopathological factors , together with 85 tumors that we reported previously . ^^^ Mutations of the EGFR and HER 2 genes were more frequently found in female never or light smoking patients with adenocarcinoma , and there were no tumors that had two or more mutations simultaneously among EGFR , HER 2 and KRAS . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In contrast , the growth of other tumor cell lines , which contained low levels of the EGFR , HER 2 , and pAkt but comparable or even higher basal levels of phosphorylated mitogen activated protein kinase ( pMAPK ) , were relatively resistant to treatment with both inhibitors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Six EGFR positive tumors were HER 2 positive . ^^^ No statistically significant differences in HER 2 status , size , lymph node status and disease free survival were observed between EGFR+ and EGFR cases , but the number of EGFR negative tumors was quite small . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Human epidermal growth factor receptor 2 ( HER 2 ) is over expressed in 15 % to 30 % of breast cancers and is a poor prognostic marker in node positive patients . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
This investigation utilizes surface plasmon resonance ( SPR ) spectroscopy to detect and quantify human epidermal growth factor receptor 2 ( HER 2 ) , an oncogene product that is over expressed in some aggressive forms of breast cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Although human epidermal growth factor receptor 2 ( HER 2 ) overexpression is implicated in tumor progression for a variety of cancer types , how it dysregulates signaling networks governing cell behavioral functions is poorly understood . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : The studies described here are intended to characterize the ability of BMS 599626 , a small molecule inhibitor of the human epidermal growth factor receptor ( HER ) kinase family , to modulate signaling and growth of tumor cells that depend on HER 1 and / or HER 2 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunohistochemical study of HER 2 / neu , epidermal growth factor receptor , and steroid receptor expression in normal and malignant endometrium . ^^^ HER 2 / neu oncogene protein , epidermal growth factor receptor , progesterone receptor , and estrogen receptor were examined immunohistochemically in specimens of normal and neoplastic endometrium . ^^^ Normal endometrial epithelial cells stained with anti epidermal growth factor receptor and anti HER 2 / neu with intensities graded from 0 to 3+ . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Lapatinib is an oral dual tyrosine kinase inhibitor that targets epidermal growth factor receptor ( EGFR ) and human epidermal growth factor receptor 2 ( HER 2 ) , both frequently overexpressed in human cancer . ^^^ Preclinical data have shown that lapatinib is a potent and selective inhibitor of the tyrosine kinase domain of EGFR and HER 2 , and tumor cells that overexpress these receptors are growth inhibited by lapatinib both in vitro and in vivo . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Breast cancers with brain metastases are more likely to be estrogen receptor negative , express the basal cytokeratin CK5 / 6 , and overexpress HER 2 or EGFR . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Patients with human epidermal growth factor receptor 2 ( HER 2 ) overexpressing breast carcinomas have a more aggressive clinical behavior and their tumors are often hormone receptor negative . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The qRT PCR assays detect the human epidermal growth factor receptor 2 ( HER 2 ) and CK 20 transcripts of two tumor cells spiked into 5 mL of blood after an immunomagnetic tumor cell enrichment . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In addition , overexpression of the growth factor receptors , epidermal growth factor receptor and HER 2 / neu , was found in 9 of 18 tumors and in 6 of 13 bronchial epithelium samples . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The results indicated two subgroups of invasive ductal carcinoma ; 1 ) HER 2 / neu overexpressing cases that were negative for EGFR expression and had low proliferation fraction , and a tetraploid DNA pattern ( 22 cases ) , and 2 ) other combinations of HER 2 / neu expression and EGFR expression , with a high proliferation fraction and an aneuploid DNA pattern ( 38 cases ) . ^^^ Eight cases of carcinoma in situ were positive for HER 2 / neu overexpression and negative for EGFR expression , and had a high proliferation fraction and a tetraploid DNA pattern . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The HER 2 / neu proto oncogene is homologous with , but distinct from , the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Expression of epidermal growth factor receptor and HER 2 / neu in normal and neoplastic cervix , vulva , and vagina . ^^^ Monoclonal antibodies were used to localize immunohistochemically epidermal growth factor receptor and HER 2 / neu in normal and neoplastic frozen tissue samples from the lower genital tract of women . ^^^ In squamous epithelia of the cervix , vulva , and vagina , epidermal growth factor receptor and HER 2 / neu both were expressed most strongly by basal keratinocytes . ^^^ In contrast , both epidermal growth factor receptor and HER 2 / neu were expressed throughout the entire thickness of the epithelium by undifferentiated squamous cells in squamous metaplasia , raised condyloma , and carcinoma in situ . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The HER 2 / neu oncogene ( a member of the Erb like oncogene family ) is distinct from but closely related to the c erb B gene which encodes the epidermal growth factor receptor ( EGFr ) . ^^^ Preliminary evaluation of HER 2 / neu oncogene and epidermal growth factor receptor expression in normal and neoplastic human ovaries . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Amplification of HER 2 / neu , a protooncogene related to the epidermal growth factor receptor , has prognostic significance in patients with breast cancer . ^^^ We have addressed the question of whether amplification of HER 2 / neu or epidermal growth factor receptor occurs in DNA from human endocrine tumor lines and have sought to characterize the HER 2 / neu gene and its products in carcinoid tumors of the gut . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Continued expression of the epidermal growth factor receptor , new expression of c fms , and overexpression of HER 2 / neu are associated with a poor prognosis . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The HER 2 / neu oncogene ( a member of the Erb like oncogene family ) is distinct from but closely related to the c erb B gene which encodes the epidermal growth factor receptor ( EGFr ) . ^^^ Preliminary evaluation of HER 2 / neu oncogene and epidermal growth factor receptor expression in normal and neoplastic human ovaries . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Prognostic indicators for neuroblastoma : stage , grade , DNA ploidy , MIB 1 proliferation index , p 53 , HER 2 / neu and EGFr a survival study . ^^^ The features studied were : stage , Shimada classification , DNA ploidy , MIB 1 proliferation index and status for HER 2 / neu , p 53 and epidermal growth factor receptor ( EGFr ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
To identify and modulate molecular SEBs in intraepithelial neoplasia of the upper aerodigestive tract , we studied expression of the epidermal growth factor receptor ( EGFR ) , transforming growth factor alpha ( TGF alpha ) , and HER 2 / neu genes in oral leukoplakia before , during , and after treatment with 13 cis retinoic acid , a vitamin A derivative . ^^^ Pretreatment expression of EGFR , TGF alpha , and HER 2 / neu in leukoplakia was increased when compared to normal appearing mucosa . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Although its function in the HER 2 / neu promoter is unknown , this purine rich site is homologous to a protein binding sequence in the promoter of the epidermal growth factor receptor that is necessary for efficient transcription of this gene . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The HER 2 / neu oncogene is a member of the erbB like oncogene family , and is related to , but distinct from , the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
METHODS : We have examined 285 breast biopsy specimens ( 140 benign , 145 malignant ) for DNA ploidy , S phase fraction , Ki 67 nuclear antigen proliferative indices , and HER 2 / neu and epidermal growth factor receptor oncoproteins . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Ploidy , S phase fraction , Ki 67 staining , estrogen receptor ( ER ) , progesterone receptor ( PR ) , and the expression of HER 2 / neu and epidermal growth factor receptor ( EGFR ) were evaluated in these tumors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Time resolved immunofluorometric procedures were used to quantify both p 53 protein and PSA in 200 breast tumour extracts , which were also assayed for oestrogen ( ER ) and progesterone receptors ( PGR ) , epidermal growth factor receptors ( EGFR ) , cathepsin D and HER 2 / neu , and characterised for S phase fraction and DNA ploidy . ^^^ Contingency tables indicated significant negative associations between the status of p 53 and that of ER ( P = 0 . 003 ) and PGR ( P = 0 . 001 ) and between PSA and S phase fraction ( P = 0 . 012 ) , and positive associations between p 53 and EGFR ( P = 0 . 017 ) , HER 2 / neu ( P = 0 . 008 ) , S phase fraction ( P = 0 . 001 ) and aneuploidy ( P = 0 . 007 ) , and between PSA and both ER ( P = 0 . 061 ) and PGR ( P = 0 . 010 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The fact that these HER 2 / neu peptide reactive CTL show significantly lower reactivity with corresponding EGF R peptides offers new perspectives for understanding the recognition of self antigens by tumor reactive T cells . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The predictive value of the presence of hormone receptors in tumors is associated with a favorable disease free and overall survival difference of 8 10 % ; however , this advantage is being eroded by the early appearance of other factors , such as the epidermal growth factor receptor ( EGFR ) , proliferative capacity ( S phase ) , nuclear grade , and HER 2 / neu oncogene . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Fifty six specimens of gastric carcinoma were examined for the localization of HER 2 / neu oncoprotein ( HER 2 / neu ) and epidermal growth factor receptor ( EGFR ) by immunohistochemistry using polyclonal antibodies on paraffin embedded material . ^^^ Patchy staining was common for HER 2 / neu , while EGFR immunoreactivity was always diffuse . ^^^ Twenty cases ( 35 . 7 % ) showed positive staining for both , 15 cases ( 26 . 8 % ) for HER 2 / neu only , four cases ( 7 . 1 % ) for EGFR only , and 17 cases ( 30 . 4 % ) for neither . ^^^ The EGFR positivity did not further reduce survival in HER 2 / neu positive cases ( 362 days ) . ^^^ Our findings also suggest that expression of these two closely related protooncogenes in malignant and benign gastric tissues is independent of each other and that EGFR does not potentiate the oncogenic effect of HER 2 / neu . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunohistochemical staining for p 53 , HER 2 / neu , estrogen receptor , progesterone receptor , and epidermal growth factor receptor was performed on frozen sections from 100 primary endometrial cancers . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Expression of EGFR , HER 2 / neu , P 53 , and PCNA in endometrioid , serous papillary , and clear cell endometrial adenocarcinomas . ^^^ Immunohistochemical stains were employed to detect the presence of epidermal growth factor receptor ( EGFR ) , HER 2 / neu , p 53 , and proliferating cell nuclear antigen ( PCNA ) . ^^^ Analysis revealed that EGFR was expressed in 49 % , HER 2 / neu in 59 % , p 53 in 9 % , and PCNA in 16 % of tumor specimens . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
SUMMARY BACKGROUND DATA : Amplification of HER 2 / neu , a proto oncogene related to the epidermal growth factor receptor , and mutation of the ras proto oncogene and p 53 tumor suppressor gene appear to play a role in the pathogenesis of some human cancers . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Fine needle aspirates ( FNA ) from 106 high risk women and 25 low risk women were evaluated for overexpression of estrogen receptor ( ER ) , epidermal growth factor receptor ( EGFR ) , mutant p 53 , and HER 2 / neu by immunocytochemistry , and for aneuploidy by image analysis . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Both epidermal growth factor receptor ( EGFR ) and HER 2 / neu ( neu ) have been found to be of prognostic importance in epithelial ovarian and endometrial carcinoma , but alterations in proto oncogene expression of normal tissues of patients with gynecologic malignancies are unknown . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
A poor clinical prognosis is associated with expression or overexpression of the epidermal growth factor receptor , fms , and HER 2 / neu . ^^^ Coexpression of HER 2 / neu and the epidermal growth factor receptor has been observed in 65 % of epithelial ovarian cancers and in a limited number of normal tissue from a fraction of donors . ^^^ The extracellular domains of the HER 2 / neu gene product p 185 and the epidermal growth factor receptor may provide useful targets for serotherapy . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunohistochemistry was used to grade overexpression of p 53 protein , HER 2 / neu protein , epidermal growth factor receptor ( EGFR ) , and Ki 67 antigen in both the glands and stroma of tissue from 20 women with MMMT and 6 women with AS . ^^^ The expression of epidermal growth factor receptor , HER 2 / Neu , p 53 , and Ki 67 antigen in uterine malignant mixed mesodermal tumors and adenosarcoma . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
It is now clear that the growth of breast cancer is regulated by growth factor receptors ( eg , EGFR and Her 2 / neu ) , and that their upregulation is associated with impaired prognosis . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Age , age at menarche , number of lymph nodes with metastasis , estrogen and progesterone receptor levels , ploidy status , S phase , Ki 67 , HER 2 / neu expression , tumor grade , epidermal growth factor receptor expression , lipid associated sialic acid ( LASA ) , and carcinoembryonic antigen level were not significantly related to ethnicity . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Specimens from 22 patients with tumors of borderline malignancy ( 11 serous and 11 mucinous tumors ) , 12 patients with benign tumors , and 16 patients with invasive ovarian carcinomas were evaluated for expression of epidermal growth factor receptor ( EGFR ) , HER 2 / neu , PTP1B , and p 53 by immunohistochemical techniques . ^^^ One or both of the tyrosine kinase growth factor receptors EGFR and HER 2 / neu was expressed by 42 % of benign , 59 % of borderline , and 81 % of malignant ovarian tumors . ^^^ However , among 12 tumors with PTP1B expression , 9 also expressed EGFR or HER 2 / neu . ^^^ Either EGFR or HER 2 / neu was detected in a majority of borderline cancers . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In this study , we have measured PSA , IGF 1 , IGF 2 , IGFBP 1 and IGFBP 3 in tumour tissue cytosols from 200 women with primary breast cancer , and have examined relationships between IGFs or IGFBPs and PSA along with other markers , including p 53 protein , steroid hormone receptors ( oestrogen and progesterone ) , cathepsin D , epidermal growth factor receptor , Her 2 / neu protein , S phase fraction and DNA ploidy . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Examination for the localization of epidermal growth factor receptor ( EGF R ) and HER 2 / neu oncoprotein by immunohistochemistry revealed positive staining on the epithelial strands branching downwards on the specimens of seborrheic keratoses . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Using immunocytochemistry , tumors were stained for overexpression of HER 2 / neu , epidermal growth factor receptor ( EGFR ) , p 53 , tumor necrosis factor alpha ( TNF alpha ) , and Ki 67 ( a marker of cellular proliferation ) . ^^^ HER 2 / neu was overexpressed in 7 cases ( 11 % ) , EGFR in 12 cases ( 19 % ) , and p 53 in 32 cases ( 50 % ) . ^^^ Comparison between tumors that did or did not overexpress p 53 revealed insignificant differences in the expression of HER 2 / neu , EGFR and TNF alpha . ^^^ Comparison of tumors with high Ki 67 indices to those with lower indices also revealed no association with the expression of HER 2 / neu , or EGFR , and there were no differences in stage or grade distribution . ^^^ Overexpression and relationships of HER 2 / neu , epidermal growth factor receptor , p 53 , Ki 67 , and tumor necrosis factor alpha in epithelial ovarian cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In a prospective pilot study , we performed breast fine needle aspirations ( FNAs ) on 213 high risk and 30 low risk women and analyzed these aspirates for cytologic changes and biomarker abnormalities of aneuploidy and overexpressed estrogen receptor ( ER ) , epidermal growth factor receptor ( EGFR ) , p 53 and HER 2 / neu . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
OBJECTIVES : Our purpose was to determine the molecular profile of advanced stage transitional cell carcinoma in terms of immunostaining for p 53 , epidermal growth factor receptor and HER 2 / neu , deoxyribonucleic acid index , and S phase fraction and to analyze the prognostic significance of these markers . ^^^ Selected sections of the primary tumors were immunostained for p 53 , epidermal growth factor receptor , and HER 2 / neu ; deoxyribonucleic acid ploidy and S phase fraction were determined with use of flow cytometry . ^^^ RESULTS : Positive immunostaining was observed for p 53 in 13 cases ( 45 % ) , for epidermal growth factor receptor in 14 cases ( 50 % ) , and for HER 2 / neu in 19 cases ( 65 % ) . ^^^ CONCLUSION : Neither immunostaining for p 53 , epidermal growth factor receptor , and HER 2 / neu nor deoxyribonucleic acid ploidy nor S phase fraction allowed us to distinguish transitional cell carcinoma from other more common epithelial ovarian cancers . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : The HER 2 / neu gene codes for a membrane receptor protein that is homologous , but distinct from the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunohistochemical staining was performed for Ki 67 , proliferating cell nuclear antigen ( PCNA ) , epidermal growth factor receptor ( EGFR ) , HER 2 / neu encoded receptor protein , p 53 gene product , and multidrug resistance gene product ( P glycoprotein ) . ^^^ The expression of EGFR , HER 2 / neu encoded receptor protein , and mutant p 53 product was significantly lower in LMP tumors than in carcinomas ( p < 0 . 05 ) . ^^^ Immunohistochemical detection of EGFR , HER 2 / neu , and p 53 in ovarian epithelial tumor is relevant to ovarian tumorigenesis . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The Her 2 / neu oncogene encodes a Mr 185 , 000 transmembrane protein with homology to the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Correlated cellular measurements of cell DNA content , Her 2 / neu , epidermal growth factor receptor ( EGFR ) , and p21ras levels were performed on each of 5 , 000 to 100 , 000 cells from each tumor . ^^^ When the data were treated as correlated intracellular measurements , 90 of the 94 tumors studied contained a population of cells in which the intracellular levels of Her 2 / neu expression were directly correlated with the levels of EGFR expression in the same cells . ^^^ The ratio of Her 2 / neu molecules to EGFR molecules in the same cells exceeded 1 in the majority of tetraploid and aneuploid cases and was close to or less than 1 in the majority of diploid cases . ^^^ In nearly all tumors , p21ras overexpression was observed only in cells that overexpressed Her 2 / neu , EGFR , or both , and p21ras levels per cell were more closely correlated with levels of EGFR per cell in the same cells than with Her 2 / neu levels per cell . ^^^ The data are consistent with a model in which heterodimerization of Her 2 / neu and EGFR in individual cells is achieved by one of several genetic evolutionary pathways , all of which commonly lead to p21ras overexpression . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In a prospective pilot study , we performed breast fine needle aspirations ( FNAs ) on 224 high risk and 30 low risk women and analyzed these aspirates for cytologic changes and biomarker abnormalities of aneuploidy and overexpressed estrogen receptor ( ER ) , epidermal growth factor receptor ( EGFR ) , p 53 and HER 2 / neu . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The HER 2 / neu oncogene encodes a transmembrane tyrosine kinase receptor with extensive homology to the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In breast cancer , these molecular targets have included principally tumor associated antigens , such as carcinoembryonic antigen ( CEA ) and the polymorphic epithelial mucin antigen , MUC 1 , and more recently the growth factor receptors , EGF R and HER 2 / neu . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
OBJECTIVE : To study EGF R , HER 2 / neu ( p 185 ) , p 53 , Mib 1 ( Ki 67 ) , Bax , Bcl 2 , ras expression and ploidy in borderline tumors of the ovary by assessing their frequency , and relationship to histologic type , tumor recurrence and survival . ^^^ Paraffin embedded sections were stained using monoclonal antibodies against EGF R , HER 2 / neu ( p 185 ) , p 53 , Mib 1 ( Ki 67 ) , Bax , Bcl 2 , and ras . ^^^ CONCLUSION : The data demonstrate expression of EGF R , p185 / HER 2 / neu , p 53 , Mib 1 ( Ki 67 ) , Bax , Bcl 2 , and ras in a subgroup of patients with ovarian borderline tumors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The HER 2 / neu oncogene encodes a transmembrane tyrosine kinase receptor with extensive homology to the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The HER 2 / neu oncogene encodes a transmembrane tyrosine kinase receptor with extensive homology to the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunohistochemistry was also used to examine the expression of proliferating cell nuclear antigen ( PCNA ) , epidermoid growth factor receptor ( EGFR ) , HER 2 / neu , and p 53 in the pathological sections . ^^^ TNM tumor staging , the number of diseased lymph nodes ( N < or = 3 or N > 3 ) , degree of cell differentiation , DNA ploidy , SPF , and lymphovascular invasion were more useful than biological markers , such as PCNA , EGFR , HER 2 / neu , and p 53 , for the prognosis of ESCC . ^^^ The prognostic value of biological markers , including PCNA , EGFR , HER 2 / neu , and p 53 , however , is limited . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Novel targets for which advances are being made include the following : growth factor receptor tyrosine kinases such as the epidermal growth factor receptor and HER 2 / neu ( proliferation ) ; the vascular endothelial growth factor receptor and the basic fibroblast growth factor receptor ( angiogenesis ) ; the oncogenic GTP binding protein Ras ( especially agents targeting Ras farnesylation , farnesyltransferase inhibitors ) ( proliferation ) ; protein kinase C ( proliferation and drug resistance ) ; cyclin dependent kinases ( proliferation ) ; and matrix metalloproteinases and angiogenin ( angiogenesis and metastasis ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The HER 2 / neu oncogene , localized to chromosome 17q , shares substantial homology with the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
MARY 10 was estrogen receptor , progesterone receptor , Her 2 / neu negative and p 53 , epidermal growth factor receptor positive . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Many tyrosine kinases , such as the epidermal growth factor receptor , Her 2 / Neu , Src , and Axl , are known to play a role in oncogenic signals in transformed cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Cross reactivity with human epidermal growth factor receptor , which has extensive homology with HER 2 / neu extracellular domain , was < 0 . 6 % . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Overexpressions of epidermal growth factor receptor ( EGFR ) and HER 2 / neu have been reported to affect the sensitivity of certain human cancer cells to cisplatin , presumably by modification of DNA repair activity through interference with NER . ^^^ The interrelationships between NER activity , cisplatin sensitivity , HER 2 / neu expression and EGFR level , were also analyzed . ^^^ The finding that high levels of EGFR showed very little influence on the relationship between p185neu and cisplatin resistance suggests that EGFR may be a less crucial factor in modulating the chemoresistance of NSCLC cells when compared with HER 2 / neu . . ^^^ Interrelationships between cellular nucleotide excision repair , cisplatin cytotoxicity , HER 2 / neu gene expression , and epidermal growth factor receptor level in non small cell lung cancer cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In a prospective random fine needle aspiration ( FNA ) study of women at high risk of development of breast cancer , we previously demonstrated that cytologic evidence of epithelial hyperplasia with or without atypia , as well as abnormalities of several cellular biomarkers ( DNA ploidy ; immunocytochemical expression of p 53 , EGFR , ER , and / or Her 2 / neu ) , were more prevalent in high risk women than in low risk controls . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The identification of specific molecular abnormalities ( HER 2 / neu or epidermal growth factor receptor [ EGFR ] overexpression ) led to the development of targeted therapeutic intervention ( monoclonal antibodies and tyrosine kinase inhibitors ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
HER 2 / neu is a 185 kDa glycoprotein related to the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Immunotherapy using a monoclonal antibody against the human epidermal growth factor receptor 2 protein , HER 2 / neu , has proven to be clinically efficacious in about one half of breast cancer patients who exhibit strong ( 3+ ) plasmalemmal immunoreactivity for this protein . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
METHODS : To determine the prognostic value of the urokinase plasminogen activation system , contents of uPA , uPAR , and PAI 1 were measured in extracts of endometrial cancer tissue using ELISAs . uPA , uPAR , and PAI 1 levels were determined in 91 , 54 , and 92 extracts , respectively , and correlated with tumor histology , stage , grade , lymph node involvement , prevalence of metastasis , and recurrence as well as with estrogen ( ER ) , progesterone ( PR ) , epidermal growth factor ( EGFR ) receptor and HER 2 / neu contents . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Baseline multidrug resistance protein ( MRP ) , Her 2 / neu , and epidermal growth factor receptor ( EGFR ) expression , and pre and posttherapy bax and bcl 2 expression were determined by Western blot analysis . p 53 status was determined by sequencing . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The HER 2 / neu oncogene is localized to chromosome 17q and shares significant homology with the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Since the overexpression of certain growth factors and / or their receptors , such as vascular endothelial growth factor ( VEGF ) , epidermal growth factor receptor ( EGFR ) and HER 2 / neu , as well as various oncogenes like c fos and c jun , is associated with unfavorable prognosis and contributes to progressive growth of ovarian carcinomas , their mRNA levels were analyzed by RT PCR . ^^^ Conversely , DOX decreased non significantly the expression levels for EGFR by 32 % , VEGF 35 % , both c fos and c jun approximately 20 % and HER 2 / neu by only 15 % . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We evaluated epidermal growth factor receptor ( EGFR ) , HER 2 / neu , matrix metalloproteinase ( MMP ) 2 , MMP 9 , p 53 and bcl 2 expression and microvessel density ( MVD ) in patients who underwent surgery with curative intent in our department between 1991 and 1996 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Interphase fluorescent in situ hybridization ( FISH ) was performed on 5 microm microarray sections using pericentromeric probes to chromosomes 7 , 8 , and 17 and probes for the HER 2 / neu and epidermal growth factor receptor ( EGFR ) genes . ^^^ Aneusomy of chromosomes 7 , 8 , and 17 and amplification of HER 2 / neu and epidermal growth factor receptor in Gleason score 7 prostate carcinoma : a differential fluorescent in situ hybridization study of Gleason pattern 3 and 4 using tissue microarray . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We sought to determine the effects of treatment with a specific COX 2 inhibitor and / or a monoclonal antibody against the ErbB receptor subtype HER 2 / neu on carcinoma cell growth . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Overexpression of the epidermal growth factor receptor family member Her 2 / neu in breast cancer is associated with poor prognosis . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
PURPOSE : The goal of this work was to study the expression of epidermal growth factor receptor ( by use of monoclonal antibody EGFR 1 ) and HER 2 / neu ( by use of monoclonal antibody EGFR 2 ) , as well as EGFR activation [ phosphorylated EGFR ( P EGFR ) ] and autocrine stimulation [ ligand transforming growth factor alpha ( TGF alpha ) ] markers in a series of 24 testicular tumors [ 18 nonseminomatous germ cell tumors ( GCTs ) , 1 Leydig cell tumor , and 5 seminomatous GCTs ] . ^^^ EXPERIMENTAL DESIGN : Paraffin embedded sections of tumors were studied immunohistochemically for beta human chorionic gonadotropin ( beta HCG ) , EGFR 1 , HER 2 / neu , TGF alpha , and P EGFR expression . ^^^ Expression of HER 2 / neu , TGF alpha , and P EGFR was detected in 25 , 36 , and 27 % of EGFR positive , nonseminomatous GCTs , respectively . ^^^ CONCLUSIONS : We report data , for the first time , that document EGFR and HER 2 / neu expression and indicate EGFR activation and autocrine stimulation in beta HCG positive , nonseminomatous GCTs . ^^^ These findings may be clinically relevant in relation to the recent availability of active EGFR and HER 2 / neu targeted pharmaceutical agents and to the extensively described negative prognostic significance of beta HCG expression in mixed GCTs . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
As with Her 2 / neu overexpression , overexpression of EGFR serves as a basis for specific antibody therapy in a subset of carcinomas . ^^^ Unlike Her 2 / neu , where most overexpression is secondary to gene amplification , overexpression of EGFR appears to be unrelated to gene amplification . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The HER 2 / neu oncogene encodes a transmembrane tyrosine kinase receptor with extensive homology to the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
SUCI 02 inhibited cell proliferation of HER 2 / neu overexpressing MDA MB 453m1 more potent than that of EGFR overexpressing MDA MB 468 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Cyclooxygenase 2 ( COX 2 ) , epidermal growth factor receptor ( EGFR ) , and Her 2 / neu expression in ovarian cancer . ^^^ Abnormalities of epidermal growth factor receptor ( EGFR ) and Her 2 / neu have been actively investigated in ovarian cancer and associated with unfavorable clinical outcome . ^^^ We investigated by immunohistochemistry the expression of COX 2 , EGFR , and Her 2 / neu in a series of advanced primary ovarian cancers . ^^^ Immunohistochemistry was performed on paraffin embedded sections with rabbit antiserum against COX 2 , murine monoclonal antibody ( MoAb ) 300G9 against Her 2 / neu , and monoclonal antibody 108 against EGFR . ^^^ RESULTS : No association among COX 2 , EGFR , and HER 2 / neu was found . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Many genes have been selected as targets for antisense therapy , including HER 2 / neu , PKA , TGF alpha , EGFR , TGF beta , IGFIR , P 12 , MDM 2 , BRCA , Bcl 2 , ER , VEGF , MDR , ferritin , transferrin receptor , IRE , C fos , HSP 27 , C myc , C raf and metallothionein genes . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Hormone receptor status , Ki 67 , S phase fraction , DNA ploidy , HER 2 / neu , p 53 , epidermal growth factor receptor , urokinase type plasminogen activator , plasminogen activator inhibitor 1 , bone marrow micrometastases as well as patient age , menopausal status , tumor site , tumor size , histologic type , tumor grade , carcinoma in situ , multifocality , and lymph vascular invasion ( LVI ) were studied to predict axillary lymph node status . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The higher expression of EGFr and HER 2 / neu oncoproteins in aneuploid tumors suggests that the increased proliferative activity of aneuploid carcinomas is influenced by the activity of such oncoproteins , which favors a more aggressive biological behavior . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Classes of therapeutics reviewed include those targeting tumor microenvironment interactions ( matrix metalloproteinase inhibitors , vascular endothelial growth factor blockade ) , signal transduction ( e . g . , farnesyltransferase inhibitors ) , growth factor receptors ( epidermal growth factor receptor blockade , Her 2 / neu , gastrin ) , and vaccine approaches . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Receptor tyrosine kinases ( RTKs ) such as Tie 2 , IGF1R , Her 2 / Neu , EGFR , and VEGFR 1 3 play crucial roles in the control of cell growth and differentiation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The apoptosis regulators p 53 , bcl 2 and bax , and the growth factor receptors EGFR and HER 2 / neu were analyzed by immunohistochemical techniques and DNA analysis was performed by flow cytometry . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We have investigated the protein expression pattern of the four ErbB receptors EGFR , Her 2 / neu , Her 3 and Her 4 , and correlated it with their putative ligands EGF , TGF alpha and HRG in 74 women with invasive breast cancer . ^^^ We did not observe a correlation between EGFR and Her 2 / neu or Her 4 protein expression , EGFR and Her 3 ( p = 0 . 005 ) , and Her 3 and Her 4 ( p = 0 . 05 ) were clearly co expressed . ^^^ The co expression of EGFR / Her 3 was associated with the expression of all ligands , whereas the Her 2 / neu / Her 3 was correlated with HRG ( p = 0 . 002 ) , thereby indicating a functional relation between specific receptor dimer combinations and putative ligands . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
METHODS : Specimens from 125 patients with high grade , advanced stage ( Stage 3 4 ) serous ovarian carcinoma were evaluated by immunohistochemistry for COX 2 , p 53 , bcl 2 , epidermal growth factor receptor ( EGFR ) , and Her 2 / neu expression and for CD 34 stained microvessel density ( MVD ) . ^^^ There was no association observed between COX 2 expression and expression levels of EGFR , Her 2 / neu , bcl 2 , or p 53 . ^^^ Expression of COX 2 also was correlated with tumor angiogenesis but not with EGFR , Her 2 / neu , or p 53 expression . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Promising therapeutic targets for cancer metastasis have been identified , including Src , focal adhesion kinase , the integrin receptor , the vascular endothelial growth factor receptor , the epidermal growth factor receptor , Her 2 / neu , c Met , Ras / Rac GTPases , Raf kinase , farnesyl diphosphate synthase ( i . e . , amino bisphosphonate therapeutic target ) and matrix metalloproteases within the context of their implicated functional roles in cancer growth , invasion , angiogenesis and survival at secondary sites . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The HER 2 / neu oncogene encodes a transmembrane tyrosine kinase receptor with extensive homology to the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The expression status of the estrogen receptor alpha ( ERalpha ) and that of the epidermal growth factor receptor Her 2 / neu frequently correlate inversely in breast cancers . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
BACKGROUND / AIMS : The HER 2 / neu protein is involved in normal cell proliferation and tissue growth because it is extensively homologous and related to epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
They transduced human carcinoma cells independently of the CAR pathway , via cell surface receptors targeted by specific monoclonal antibodies , that is , EGF R on A 549 , HT 29 and SW 1116 , HER 2 / neu on SK OV 3 and SK BR 3 , CA 242 ( epitope recognized by the monoclonal antibody C 242 ) antigen on HT 29 and SW 1116 , and PSMA ( prostate specific membrane antigen ) expressed on HEK 293 cells , respectively . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Thereafter , high levels of FAS are maintained in coordination with increased demand for fatty acid metabolism and / or membrane synthesis in response to cancer related overexpression of growth factors ( e . g . , EGF , heregulin ) and / or growth factor receptors ( e . g . , EGFR , Her 2 / neu ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
To this end , we have analyzed the protein expression of membrane associated epidermal growth factor receptor ( EGF R ) , Her 2 / neu , platelet derived growth factor receptor ( PDGF R ) , insulin like growth factor receptor ( IGF R ) , c Kit and of cytoplasmatic c Abl in 500 human tumors of epithelial , stromal and mesenchymal origin by immunohistochemistry , and found a distinct pattern of kinase expression : EGF R , PDGF R and c Abl were expressed in the majority of malignant tumors , whereas c Kit , Her 2 / neu and IGF R protein expression was considerably less frequent . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Accordingly , there is a need for alternate therapies , such as those recently developed against the receptor tyrosine kinases , such as epidermal growth factor receptor ( EGFR ) and HER 2 / neu . ^^^ METHODS : Archival specimens of synovial sarcoma ( n=38 ) representing 30 patients were assessed for EGFR and HER 2 / neu protein expression by standard immunohistochemical techniques . ^^^ RESULTS : EGFR and HER 2 / neu protein were detected by immunohistochemistry in 21 of 38 ( 55 . 3 % ) and 20 of 38 ( 52 . 6 % ) synovial specimens , respectively . ^^^ EGFR immunoreactivity showed a granular and membranous pattern , whereas HER 2 / neu immunoreactivity demonstrated only a membrane pattern . ^^^ Of 6 specimens with SSX 2 translocation , none ( 0 % ) showed HER 2 / neu immunoreactivity and 1 ( 17 % ) demonstrated EGFR expression . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Epidermal growth factor receptor ( EGFR ) and to a less extent , HER 2 / neu , are known to be overexpressed in non small lung cancers , but their exact status in ABAF is not well documented . ^^^ We have therefore studied the expressions of EGFR , HER 2 / neu as well as phosphorylated AKT ( pAKT ) and phosphorylated extracellular signal regulated kinase ( ERK ) , which are key molecules in these two pathways , in 15 ABAF patients . ^^^ These findings suggest that ABAF , particularly those with non mucinous histology , commonly harbors EGFR and HER 2 / neu overexpression . ^^^ PI 3K and Ras dependant pathways that lie downstream are generally activated , even in the absence of EGFR and / or HER 2 / neu overexpression . ^^^ Epidermal growth factor receptor , HER 2 / neu and related pathways in lung adenocarcinomas with bronchioloalveolar features . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Downregulation of the ErbB receptors , HER 2 / neu , and later EGFR , with monoclonal antibodies was the first demonstration of targeted therapy . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
EGFR expression did not correlate with clinical stage ( P = 0 . 361 ) , HER 2 / neu overexpression ( P = 0 . 503 ) , estrogen or progesterone receptor status ( P = 0 . 631 and P = 0 . 838 , respectively ) , nuclear grade ( P = 0 . 448 ) , or proliferative index ( P = 0 . 769 ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We studied the immunohistochemical expression of HER 2 / neu , epidermal growth factor receptor ( EGFR ) , vascular endothelial growth factor ( VEGF ) , cyclooxygenase 2 ( COX 2 ) , estrogen receptor ( ER ) , and progesterone receptor ( PR ) in uterine cervical small cell and large cell neuroendocrine carcinomas ( SCNECs and LCNECs ) from 24 patients seen at The University of Texas M . ^^^ The tumors expressing EGFR , HER 2 / neu , and COX 2 were modest in numbers : eight ( 33 . 3 % ) , 10 ( 41 . 7 % ) , and seven ( 29 . 2 % ) , respectively . ^^^ The combination of negative HER 2 / neu expression and positive EGFR expression had the worst impact on survival . . ^^^ Expression of HER 2 / neu , epidermal growth factor receptor , vascular endothelial growth factor , cyclooxygenase 2 , estrogen receptor , and progesterone receptor in small cell and large cell neuroendocrine carcinoma of the uterine cervix : a clinicopathologic and prognostic study . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Importantly , clusters of Her 2 / neu and EGFR ( erbB 1 ) co localize with lipid rafts and the lipid environment in the cell membrane of breast cancer cells profoundly influences their association properties and biological functions . ^^^ Moreover , the inhibition of FAS driven lipid rafts will also negatively affect EGFR Her 2 / neu cross talk , an important mechanism of trastuzumab resistance . ^^^ In summary , the specific blockade of a novel molecular linkage between FAS regulated membrane composition and functioning of transmembrane growth factor receptors EGFR and Her 2 / neu may represent a previously unrecognized therapeutic approach circumventing trastuzumab resistance in breast carcinomas . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The SYT SSX fusion protein that results from the 10 , 18 translocation is an appealing target , as are the proteins overexpressed in synovial sarcoma : bcl 2 , EGFR , and HER 2 / neu . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Cancer cells are known to express cell surface molecules such as specific antigens or cytokine receptors , e . g . , EGFR , Fas / CD95 , gp 100 , HER 2 / neu , IL 13Ralpha2 , and MAGE . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Overexpression of human epidermal growth factor receptor 2 ( HER 2 / neu ) characterizes a molecular subtype of breast cancer associated with poor clinical outcome . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The cells were assayed for the expression of EGFR and both cell lines express an average of 100 , 000 EGFR per cell ; however , Ishikawa H cells express higher levels of HER 2 / neu compared with Hec50co cells ( 1 . 38 10 10 ( 5 ) compared with 2 . 04 10 10 ( 4 ) , respectively ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Her 2 / neu and EGFR tyrosine kinase activation predict the efficacy of trastuzumab based therapy in patients with metastatic breast cancer . ^^^ To evaluate the effect of receptor activation on tumor response , we have investigated the phosphorylation status of Her 2 / neu and EGFR in 46 Her 2 / neu overexpressing tumor samples from trastuzumab treated metastatic breast cancer patients by immunohistochemistry . ^^^ Activated ( p ) tyr 1248 Her 2 / neu was detected in 9 of 46 breast cancers ( 20 % ) , and activated ( p ) tyr 845 and ( p ) tyr 1173 EGFR were both present in 6 tumors ( 13 % ) while EGFR was present in 16 cases ( 35 % ) . ptyr 1248 Her 2 / neu showed a trend to correlate with increased response to trastuzumab ( p = 0 . 063 ) , while ptyr 845 , ptyr 1173 EGFR and EGFR did not . ^^^ The presence of ptyr 1248 Her 2 / neu and ptyr 845 or ptyr 1173 EGFR , however , was a strong predictor of both response to trastuzumab based treatment ( OR = 8 . 0 , p = 0 . 021 and OR = 8 . 0 , p = 0 . 021 ) and clinical benefit ( OR = 5 . 47 , p = 0 . 041 and OR = 6 . 22 , p = 0 . 028 multivariate logistic regression analysis ) . ^^^ Furthermore , ptyr 845 EGFR and ptyr 1248 Her 2 / neu were both independent predictors of progression free survival ( RR = 0 . 21 , p = 0 . 01 and RR = 0 . 45 , p = 0 . 026 , multivariate analysis ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
This xenograft was ER , PR , Her 2 / neu negative and p 53 , EGFR positive . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Flow cytometric analysis was used for the detection of ER , PR , HER 2 / neu , epidermal growth factor receptor ( EGFR ) , and E cadherin . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
MATERIALS AND METHODS : To investigate this , pre treatment biopsies from 517 patients with locally advanced breast cancer were analyzed for expression of estrogen receptor [ ER ] , progesterone receptor [ PgR ] , Her 2 / neu , epidermal growth factor receptor [ EGF R ] , p 53 , Bcl 2 and MIB 1 by immunohistochemistry [ IHC ] , and these data were compared to the pathological response after preoperative epirubicine / cyclophosphamide [ EC ] chemotherapy ( + / radiotherapy ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The aims of this study were to determine the effects of ( a ) combining the epidermal growth factor receptor ( EGFR ) blocker ( erlotinib ) and the cyclooxygenase 2 inhibitor ( celecoxib ) on cell growth and apoptosis in human pancreatic cancer cell lines , ( b ) baseline EGFR expression on the potentiation of erlotinib induced apoptosis by celecoxib , and ( c ) the effects of the combination on the expression of the COX 2 , EGFR , HER 2 / neu , and nuclear factor kappaB ( NF kappaB ) . ^^^ EGFR , COX 2 , and HER 2 / neu expression was determined by Western immunoblotting . ^^^ Significant inhibition of NF kappaB activation was observed in BxPC 3 and HPAC cell lines treated with erlotinib and celecoxib . ( a ) Celecoxib can potentiate erlotinib induced growth inhibition and apoptosis in pancreatic cell lines , ( b ) high baseline EGFR expression is a predictor of this potentiation , and ( c ) the down regulation of EGFR , COX 2 , and HER 2 / neu expression and NF kappaB inactivation contributes to the potentiation of erlotinib by celecoxib . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In addition , normal and malignant liver tissues were evaluated for markers known to be involved in tumor progression and metastasis [ urokinase plasminogen activator ( uPA ) , Her 2 / neu , epidermal growth factor receptor ( EGF R ) ] using sandwich enzyme immunoassays . ^^^ While no differences were found for EGF R and Her 2 / neu , a 9 fold higher expression of uPA could be demonstrated in tumor tissue of 20 / 32 patients ( 63 % ) compared to normal liver tissue . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NHPs target various molecular pathways besides angiogenesis , including epidermal growth factor receptor ( EGFR ) , the HER 2 / neu gene , the cyclooxygenase 2 enzyme , the NF kB transcription factor , the protein kinases , Bcl 2 protein , and coagulation pathways . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
OBJECTIVE : To report the expression of estrogen receptors , progesterone receptors and human epidermal growth factor receptor ( Her 2 / neu ) in 158 Kenyan women with breast cancer and correlation with other prognostic indicators in this high risk group . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Over expression of PDGF B in 4 / 7 glioblastoma cell lines , EGFR in 1 / 7 , neu in 1 / 7 IGF 2 in 1 / 7 and ros in 2 / 7 was observed . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Expression patterns of ER alpha , PR , HER 2 / neu , and EGFR in different cell origin subtypes of high grade and non high grade ductal carcinoma in situ . ^^^ Using a panel of antibodies to ER alpha , PR , HER 2 / neu , and EGFR , along with cytokeratin ( CK ) markers ( CK5 / 6 , CK 8 , CK 14 , CK 17 , and CK 18 ) , we found that all 3 cell origin subtypes can express ER alpha and PR , and their expression is higher in non high grade DCIS than in high grade DCIS ; the expression of HER 2 / neu is associated with luminal subtype only in non high grade DCIS , but can be seen in all 3 subtypes in high grade DCIS ; the expression of EGFR is low and is present only in luminal cell subtypes in both high and non high grade DCIS . ^^^ In conclusion , the expression patterns of ER alpha , PR , HER 2 / neu , and EGFR are markedly different in different cell origin subtypes of both high grade and non high grade DCIS , suggesting that cell origin subtypes as well as nuclear grade contribute to the biological and molecular heterogeneity of DCIS . . ^^^ Here we refine the relationships between these 3 subtypes and the expression patterns of estrogen receptor alpha ( ER alpha ) , progesterone receptor ( PR ) , HER 2 / neu , and epidermal growth factor receptor ( ERFR ) in 53 cases of non high grade and 46 cases of high nuclear grade DCIS . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Overexpression of the epidermal growth factor receptor family member Her 2 / neu in breast cancer leads to autophosphorylation of the receptor and induction of multiple downstream signaling pathways , including the Akt kinase to nuclear factor kappaB ( NF kappaB ) cascade that is associated with poor prognosis . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Several promising drugs targeting tyrosine kinases ( EGFR and Her 2 / Neu ) , mTOR , Raf kinase , proteasome , and histone deacetylases , as well as drugs affecting apoptosis and mitosis , are under development for clinical application . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The HER 2 / neu protein is intimately involved with normal cell proliferation and tissue growth and is extensively homologous and related to the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Comparison of each individual biomarker ' s expression from field , adjacent to tumor , and tumor , and subsequent cluster analysis of these biomarkers , indicated that the possible sequence of phenotypic expression of biomarkers in bladder cancer oncogenesis is from G actin , to p 300 antigen , to epidermal growth factor receptor ( EGFR ) , to p 185 ( neu oncogene product ) , to DNA aneuploidy and , finally , to visual morphology . ( ABSTRACT TRUNCATED AT 400 WORDS ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
This possibility was examined by employing a chimeric protein composed of the extracellular ligand binding domain of the epidermal growth factor receptor and the neu cytoplasmic portion . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The protein product of the neu protooncogene , p185c neu , is structurally similar to the epidermal growth factor receptor ( EGFR ) . ^^^ Heterodimerization of p185c neu and EGFR occurs in M 1 cells , which express both receptors . ^^^ We have individually identified the two components of the heterodimer as EGFR and p185c neu . ^^^ These results indicate that the physical association between EGFR and p185c neu is of functional significance and define enzymatic features of complex receptor formation . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
To circumvent the use of the incompletely characterized ligand of Neu , we constructed a chimeric protein composed of the ligand binding domain of the epidermal growth factor receptor and the transmembrane and cytoplasmic portions of Neu . ^^^ By expressing this Neu epidermal growth factor receptor chimera ( termed NEC ) , we found that following stimulation by the heterologous ligand , the tyrosine kinase of Neu became associated with a phosphatidylinositol ( PI ) kinase activity . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
A chimeric EGFR / neu receptor in functional analysis of the neu oncoprotein . ^^^ In the future we plan to focus on characterization of possible differences between EGFR and neu signalling in more differentiated cellular backgrounds . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The rat neu oncogene encodes a constitutively activated growth factor receptor / transmembrane tyrosine kinase , p185Tneu , that is structurally similar to yet distinct from the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
To study the implications of the oncogenic mutation and the consequent receptor dimerization on the interaction with the yet incompletely characterized ligand of p185neu , we constructed chimeric proteins between the ligand binding domain of the epidermal growth factor receptor and the transmembrane and cytoplasmic domains of the normal or the transforming Neu proteins . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The erb B2 / neu oncogene encodes a protein which sequence is closely similar to the epidermal growth factor receptor ( EGFR ) . ^^^ Thus , the expression of both erbB 1 / EGFR gene and erbB 2 / neu oncogene can be induced by EGF . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The oncogene probes utilized were N and H ras , sis , EGF R ( erb B 1 ) , neu ( erb B 2 ) , fos , N and c myc , mos , and yes . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Expression during Drosophila development of DER , a gene related to erbB 1 and neu : correlations with mutant phenotypes . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The rat neu gene product is a 185 kD membrane bound tyrosine kinase that is closely related to , yet distinct from the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Both neu and epidermal growth factor receptor ( EGFR ) appear to have a close correlation between overexpression of the gene product and outcome of disease in breast cancer ; valuable information for prognosis of the disease . ^^^ Current assays available , an ELISA for Neu and a radio ligand binding assay for EGFR , are highly sensitive , reproducible and relatively easy to perform . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Tyrosine phosphorylated proteins were similar but not identical in epidermal growth factor ( EGF ) stimulated cells expressing the human EGF receptor ( EGFR ) or a chimeric EGFR / neu receptor but differed from phosphotyrosyl proteins constitutively expressed in neu oncogene transformed cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Formalin fixed paraffin embedded tumor tissue from 51 node positive breast cancer patients were analyzed for the expression of neu , epidermal growth factor receptor ( EGF R ) , and transforming growth factor alpha ( TGF alpha ) using immunoperoxidase staining . ^^^ A significant correlation between neu and EGF R expression was also noted . ^^^ Tumors expressing membranous staining of neu had a greater than 70 % chance of expressing EGF R ( P less than 0 . 01 ) . ^^^ Expression of neu protein , epidermal growth factor receptor , and transforming growth factor alpha in breast cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The Drosophila epidermal growth factor receptor homolog ( DER ) displays sequence similarity to both the epidermal growth factor ( EGF ) receptor and the neu vertebrate proteins . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The neu oncogene protein , p 185 , and epidermal growth factor receptor ( EGFR ) were localized immunohistochemically in benign and malignant human breast tissues using monoclonal antibodies . ^^^ At the cellular level , heterogenous expression of p 185 and EGFR was occasionally observed in both benign and malignant tissues , and a single case of cancer overexpressing both neu and EGFR showed reciprocal patterns of staining , indicating their independent expression . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The epidermal growth factor receptor and the product of the neu protooncogene are members of a receptor tyrosine phosphorylation cascade . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Some endometrial cancers and endometrial adenocarcinoma cell lines show amplified expression of proto oncogenes ( fos , fms , myc , myb , neu , and erb B ) and augmented production of growth factors ( colony stimulating factor 1 , epidermal growth factor , transforming growth factor alpha , and transforming growth factor beta ) and epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The specificity and sensitivity of the molecular and immunologic probes for neu were established with the use of genetically engineered cell lines that overexpressed either neu or epidermal growth factor receptor ( EGFR ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The neu oncogene codes for a cell surface protein that has a high degree of homology with the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Epidermal growth factor receptor ( EGFr ) as a marker for poor prognosis in node negative breast cancer patients : neu and tamoxifen failure . ^^^ Epidermal growth factor receptor ( EGFr ) as a marker for poor prognosis in node negative breast cancer patients : neu and tamoxifen failure . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Probes utilized represent 11 known oncogenes ( erbB 1 , gli , neu , myc , L myc , N myc , H ras , K ras , N ras , sis , and src ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The neu gene ( also called NGL , erbB 2 , and HER 2 ) encodes a 185 190 kDa transmembrane glycoprotein , p185neu , which has tyrosine specific kinase activity and is homologous to but distinct from the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Expression of neu conferred similar poor prognosis to EGFR expression in all prognostic subgroups . ^^^ Coexpression of neu and EGFR had an additive adverse effect . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Southern blot analysis of primary NIH3T3 transformant DNAs carrying oncogenes from radiation initiated squamous cell carcinomas indicated that the oncogenes responsible for the transformation of the recipient cells were not Ha ras , Ki ras or N ras genes , nor were they erbB , B lym , met , neu or raf . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The rat neu gene , which encodes a protein closely related to the epidermal growth factor receptor , is a proto oncogene that can be converted into an oncogene by a point mutation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Receptor downregulation and DNA synthesis are modulated by EGF and TPA in cells expressing an EGFR / neu chimera . ^^^ EGF was used to stimulate a chimeric receptor consisting of the epidermal growth factor receptor ( EGFR ) extracellular , transmembrane , and protein kinase C substrate domains linked to the intracellular tyrosine kinase and carboxyl terminal domains of the rat neu protein in NIH / 3T3 cells . ^^^ EGF bound to the cells was rapidly internalized in a complex with the EGFR / neu protein , as shown by loss of EGF binding and EGFR antigens from the cell surface . ^^^ The movement of the EGFR / neu protein was followed with indirect immunofluorescence into a vesicular intracellular compartment using antibodies against both EGFR and neu protein domains . ^^^ These results show that the chimeric EGFR / neu receptor undergoes typical downregulation upon ligand binding and TPA pretreatment and is capable of transducing an EGF induced mitogenic signal . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Furthermore , amplification of neu and the epidermal growth factor receptor gene could be detected in as few as 100 breast carcinoma cells or in single sections of formalin fixed , embedded material . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
One proto oncogene , Erbb 2 ( analogous to the neu proto oncogene ) , and one growth factor locus , Csfg ( granulocyte colony stimulating factor ) , which had not been mapped in the mouse were also localized on Chromosome 11 using the interspecific backcross mice . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
However , the neu oncogene and the gene encoding the EGFR have been shown to reside on distinct chromosomes . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The rat neu gene , which encodes a receptor like protein homologous to the epidermal growth factor receptor , is frequently activated by a point mutation altering a valine residue to a glutamic acid residue in its predicted transmembrane domain . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The neu oncogene , identified in ethylnitrosourea induced rat neuroglioblastomas , had strong homology with the erbB gene that encodes the epidermal growth factor receptor . ^^^ The neu gene : an erbB homologous gene distinct from and unlinked to the gene encoding the EGF receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Its primary sequence is very similar to that of the human epidermal growth factor receptor and the 5 erbB oncogene product ; the chromosomal location of the gene for this protein is coincident with the neu oncogene , which suggests that the two genes may be identical . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The neu gene is distantly related to the erbB gene and encodes a cell surface protein that appears to function as a growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The deduced amino acid sequence shows a similar degree of homology to the human epidermal growth factor receptor and to the rat and human neu proteins ; the most striking difference is the addition of a third cysteine rich extracellular domain in DER . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The rat p185c neu and the epidermal growth factor receptor ( EGFR ) can associate into an active heterodimeric tyrosine kinase . ^^^ We now show that mutant Neu proteins resulting from a point mutation at the ATP binding site ( N 757 ) or cytoplasmic domain deletions ( N691stop ) are still able to undergo EGF induced heterodimerization with EGFR . ^^^ Analysis of heterodimer formation between EGFR and truncated Neu proteins revealed that heterodimerization is preferred over homodimerization of EGFR . ^^^ These results provided evidence that the Neu ectodomain is sufficient to associate with EGFR physically , and the cytoplasmic domain interaction is required for heterodimeric kinase activation , indicating that Neu / c erbB 2 is not just a simple substrate for EGFR but a transactivator as well . . ^^^ Heterodimerization of epidermal growth factor receptor and wild type or kinase deficient Neu : a mechanism of interreceptor kinase activation and transphosphorylation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Studies of mRNA from CWR 22 have demonstrated the expression of prostate specific antigen and the epidermal growth factor receptor family including erbB1 / epidermal growth factor receptor , erbB2 / neu , and erbB 3 , but not erbB 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Southern blot analysis of transformant DNAs showed that the transforming activity was not due to the acquisition of a ras ( Ha , Ki , or N ) , neu , myc , A raf , 5 raf , erbA , or erbB gene of rat origin . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Replication defective retroviruses expressing the t neu oncogene , or a hybrid protein with the neu tyrosine kinase linked to the external region of the human epidermal growth factor receptor ( egfr neu ) , were used to establish lines of murine oligodendroglial precursor cells . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
A kinase associated with chromatin that can be activated by ligand p185c Neu or epidermal growth factor receptor interactions . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Transcripts coding for transcription factors ( RB , P 53 , FOS , MYC , MYB , ERBA , REL ) , growth factors ( FGF 1 , FGF 2 , INT 2 , TGFA , TGFB , PDGF , IGF 1 , IGF 2 ) , interleukins , ( IL 1 , IL 2 , IL 3 , IL 4 , IL 6 , TNF ) , growth factor receptors or cytosolic protein kinases ( RAF , PIM , FES , MET , SRC , ROS , TRK , KIT , CSFR , IGFR , PDGFR , EGFR , NEU ) were quantified in cultured human mammary fibroblasts from normal tissues , benign tumours , carcinomas and post radiation fibrosis lesions by slot blot autoradiography and image analysis . ^^^ The drugs modulated the levels of the anti oncogene transcripts ( RB , P 53 ) and of ERBA , REL , RAF , MET , ROS , TRK , CSFR , EGFR , NEU , FGF 1 , INT 2 , IGF 1 , IL 1 , IL 2 , IL 4 and IL 6 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The serum concentrations of TNF alpha correlated moderately with cancer ( r = 0 . 3 ) , lung cancer ( r = 0 . 3 ) , and Neu oncoproteins and epidermal growth factor receptor ( EGFR ) ( r = 0 . 3 , 0 . 5 respectively ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NIH3T3 transformants from a tertiary round of transfection were analysed by Southern blot analysis for the presence of Ki ras , N ras , raf , trk , abl , fms , src , mos , fos , sis , fps , erbA , erbB or neu oncogenes of REC origin , and none were detected . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Kinase deficient neu proteins suppress epidermal growth factor receptor function and abolish cell transformation . p185c neu and epidermal growth factor receptor ( EGFR ) associate into an active heterodimer , and overexpression of these two receptors leads to a transformed phenotype . ^^^ However , the association of EGFR and kinase deficient Neu proteins ( point mutant N 757 or cytoplasmic domain deletion mutant N691stop ) results in a defective or inactive heterodimeric complex . ^^^ In this report we explore the biological consequences of heterodimerization between EGFR and wild type ( WT ) or kinase deficient mutant Neu proteins in living cells . ^^^ We show that co expression of EGFR and kinase deficient Neu proteins abolished the synergistic transformation and tumorigenicity . ^^^ These results provide the first evidence that kinase deficient Neu proteins suppress normal EGFR function and display a dominant negative mutant phenotype . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The neu receptor which has a 50 % homology with EGF R was , however , absent from the glomerulus and cultured mesangial cells did not express detectable levels . ^^^ Despite its homology with EGF R , the neu receptor is unlikely to have similar importance . . ^^^ An immunohistological study of epidermal growth factor receptor and neu receptor and neu receptor expression in proliferative glomerulonephritis . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We also tested the effect of ketoepoxides on in vitro epidermal growth factor receptor and neu tyrosine kinase activities . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Neu differentiation factor ( NDF , also called heregulin ) was isolated from mesenchymal cells on the basis of its ability to elevate phosphorylation of ErbB proteins . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The rat neu protooncogene encodes a 185 kD transmembrane protein ( p185neu ) , which is a member of the epidermal growth factor receptor ( EGFr ) family . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The rat neu oncogene encodes a growth factor receptor like glycoprotein , termed p 185 , that shares structural similarity with epidermal growth factor receptor ( EGFR ) , particularly in the tyrosine kinase domain . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The protein product of the neu ( proto ) oncogene p185neu is an analog of the epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The latter were directed against three antigenic systems [ 38 kDa glycoprotein ( gp 38 ) , epidermal growth factor receptor , and the neu oncogene product ] , which , according to their tumor selectivity , could be considered suitable for mAb guided therapy . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The expression of c fos , c jun , c ras , c erbB 1 , c neu and c myc at the protein level was investigated by immunohistochemistry . ^^^ Sixty eight percent of the tumors were positive for Fos , 40 % for Jun , 67 % for Ras , 77 % for ErbB 1 , 35 % for Neu and 39 % for Myc . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We have used a novel approach , phosphorylation sensitive anti Neu antibodies , to quantify signaling by Neu and epidermal growth factor receptor in a panel of frozen sections of mammary carcinoma specimens . ^^^ We also determined the relationship of Neu , phosphorylated Neu ( and epidermal growth factor receptor ) , and phosphotyrosine to the expression of Neu related receptors ( epidermal growth factor receptor , HER 3 , and HER 4 ) and to prognostic factors ( estrogen and progesterone receptor ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We report here that the epidermal growth factor receptor ( EGFR ) and the neu oncoprotein become rapidly tyrosine phosphorylated upon stimulation of Rat 1 cells with the GPCR agonists endothelin 1 , lysophosphatic acid and thrombin , suggesting that there is an intracellular mechanism for transactivation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Analysis of EGFR , TGF alpha , neu and c myc in 2 amino 1 methyl 6 phenylimidazo [ 4 , 5 b ] pyridine induced mammary tumors using RT PCR . 2 Amino 1 methyl 6 phenylimidazo [ 4 , 5 b ] pyridine ( PhIP ) , a mutagen found in cooked meat , has been shown to induce mammary gland tumors in rats . ^^^ In the current study , reverse transcription followed by polymerase chain reaction amplification was used to determine whether EGFR , TGF alpha , neu and c myc are differentially expressed in PhIP induced mammary gland tumors classified histologically as benign or malignant and to evaluate whether dietary fat intake influences the expression of these genes . ^^^ Of 23 total PhIP induced mammary tumors examined , 43 % , 57 % and 74 % had increased expression of EGFR , TGF alpha and neu mRNA respectively . ^^^ The percentage of dietary fat did not appear to influence the expression of EGFR , TGF alpha or neu in either tumors or mammary gland from control rats . ^^^ These results suggest that increased expression of EGFR , TGF alpha and especially neu is associated with PhIP induced mammary gland cancer in rats . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
To assess the role of receptor heterodimerization , we analyzed the ability of Neu differentiation factor ( NDF ) to induce cell growth and transformation of NIH 3T3 cells transfected with different combinations of the EGFR subfamily of receptors . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The epidermal growth factor receptor couples transforming growth factor alpha , heparin binding epidermal growth factor like factor , and amphiregulin to Neu , ErbB 3 , and ErbB 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Since the epidermal growth factor receptor ( EGFR ) and Neu are capable of forming heterodimers that are responsive to EGFR ligands such as TGF alpha , we examined whether coexpression of TGF alpha and Neu in mammary epithelium could cooperate to accelerate the onset of mammary tumors . ^^^ Immunoprecipitation and immunoblot analyses with EGFR and Neu specific antisera , however , failed to detect physical complexes of these two receptors . ^^^ Taken together , these observations suggest that Neu and TGF alpha cooperate in mammary tumorigenesis through a mechanism involving Neu and EGFR transactivation . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The present study attempts to clarify the specific contribution of cathepsin D ( CD ) and pS 2 to the progression of breast cancer ( BC ) by examining the relationship between these two factors and TNM status , tumour grade , estradiol receptors ( ER ) and the prognosis factors epidermal growth factor receptor ( EGFR ) and neu amplification in a group of 270 BC patients . ^^^ Specific oncological contribution of cathepsin D and pS 2 in human breast cancer : their relationship with TNM status , estradiol receptors , epidermal growth factor receptor and neu amplification . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Among the oncogenes known to be important in breast cancer production are two cell surface growth factor receptors , epidermal growth factor receptor ( EGFR ) and Her 2 NEU ( NEU ) . ^^^ We examined 86 primary formalin fixed , paraffin embedded breast tumors for overexpression of EGFR and NEU and correlated our findings with the presence of cell surface phosphotyrosine as an indicator of tyrosine kinase activity at the plasma membrane . ^^^ Our data indicate that only 34 % of tumors that overexpress EGFR or NEU show plasma membrane phosphotyrosine , indicating that in the majority of these tumors , the overexpressed oncogene may not be active at this stage . . ^^^ Plasma membrane phosphotyrosine , Her 2 NEU , and epidermal growth factor receptor in human breast cancer . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Epidermal growth factor receptor ( EGFR ) / neu chimeras were used to determine if mutations that disrupt activation by Glu 664 affect hormone regulated signal transduction as well . ^^^ Epidermal growth factor receptor ( EGFR ) / neu chimeras were used to determine if mutations that disrupt activation by Glu 664 affect hormone regulated signal transduction as well . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Using this assay , we isolated a novel isoform of the proto oncogene Neu differentiation factor ( NDF ) , a ligand for erbB receptor tyrosine kinases . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We have selectively targeted the EGFr in human glioblastoma cells with kinase deficient mutants of the erbB family derived from the ectodomain of the Neu oncogene that are able to form heterodimers with EGFr and inhibit EGFr dependent phenotypes . ^^^ In EGFr positive U87MG human glioblastoma cells , expression of the Neu ectodomain inhibits EGF , but not platelet derived growth factor , induced DNA synthesis ; inhibits cell proliferation in the presence of EGF , but not platelet derived growth factor ; inhibits the ability of U87MG to form colonies in soft agar ; and inhibits transforming efficiency in athymic mice . ^^^ Neu ectodomains will be useful in determining the manner in which the EGFr contributes to glial tumorigenesis and in the design of pharmaceuticals that disable erbB family oncoproteins . ^^^ In addition , these studies provide a rationale for the application of the Neu ectodomain in gene therapy approaches to human malignant glioma and , potentially , to other systemic epithelial malignancies expressing erbB family receptors . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The following markers were selected on their putative role in the process of metastasis and were studied using immunohistochemical and / or Southern blot techniques : proliferating cell nuclear antigen ( PCNA ) , p 53 , retinoblastoma tumor suppressor gene ( Rb ) , myc , bcl 2 ( inhibitor of apoptosis ) , epidermal growth factor ( EGF ) , EGF receptor ( EGFR ) , neu , nm 23 ( also known as NME 1 , putative metastasis suppressor ) , desmoplakin , neuron cell adhesion molecule ( N CAM ) , epithelial cell adhesion molecule ( Ep CAM ) , E cadherin , cyclin D 1 ( CCND 1 ) , and EMS 1 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Prognostic significance of c erbB 2 / neu amplification and epidermal growth factor receptor ( EGFR ) in primary breast cancer and their relation to estradiol receptor ( ER ) status . ^^^ The aim of this study is to evaluate the prognostic significance of c erbB 2 / neu amplification and epidermal growth factor receptor ( EGFR ) expression in primary breast cancer ( BC ) and their prognostic implications when combined with estradiol receptor ( ER ) status . ^^^ Neu amplification was evaluated by dot blot and EGFR expression was evaluated by ligand binding assay using I 125 EGF . ^^^ Neu , EGFR , estradiol and progesterone receptors ( ER and PR ) had a marked influence on disease free survival ( DFS ) in univariate analysis . ^^^ However , in node positive ( N+ ) cases both EGFR ( p = 0 . 005 ) and neu ( p = 0 . 002 ) influenced DFS . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
These findings indicate that the products of BRCA 1 , neu , and erbB breast cancer genes participate in a common or shared signaling pathway important in cell growth and its regulation . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
As a consequence of T691stop neu expression and surface localization , cell proliferation in conditions of full growth and reduced serum and anchorage independent growth in soft agar was reduced in glioblastoma cells expressing either endogenous EGFR alone or coexpressing EGFR and elevated levels of deltaEGFRs . ^^^ T691stop neu mutant receptors abrogate the dramatic growth advantage conferred by deltaEGFR in vivo , suggesting that physical associations primarily between subdomains 3 and 4 of the p185neu and EGFR ectodomains are sufficient to modulate signaling from activated EGFR complexes . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In RINm5F cells a spectrum of erbB gene expression was detected ( EGF receptor / erbB 1 , erbB 2 / neu , and erbB 3 ) , whereas INS 1 cells showed only expression of EGF receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Concentrating on ErbB 1 and two of its ligands , epidermal growth factor ( EGF ) and transforming growth factor alpha ( TGF alpha ) , and the Neu differentiation factor ( NDF / neuregulin ) and one of its receptors , ErbB 3 , we show that ligand binding variably accelerates endocytosis of the respective ligand receptor complex . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Furthermore , the SH 2 domain inhibited focus formation by the Neu oncoprotein , another EGFR family member . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Expression of Neu was always accompanied by co overexpression of the endogenous epidermal growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
OBJECTIVES : Epidermal growth factor receptor ( EGFR ) and oncogene Neu belong to a family of growth factor receptors which may play a part in carcinogenesis . ^^^ Although increased serum concentrations of Neu and EGFR have been shown in several patients with asbestosis who later developed cancer , serum concentrations have not been studied in workers exposed in the past to asbestos but without asbestos related diseases . ^^^ Pleural plaques predicted lower serum concentrations of EGFR but not lower Neu concentrations , and this finding remained significant after adjustment for age , exposure time , smoking , and time from initial exposure . ^^^ CONCLUSIONS : Enhanced secretion of EGFR and Neu was found in a large cohort of retired asbestos workers with a wide range of exposure and latency periods . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
We expressed the epidermal growth factor receptor ( EGFR ) along with mutant p 185 ( neu ) proteins containing the rat transmembrane point mutation . ^^^ Co expression of full length EGFR and oncogenic p 185 ( neu ) receptors resulted in an increased EGF induced phosphotyrosine content of p 185 ( neu ) , increased cell proliferation to limiting concentrations of EGF , and increases in both EGF induced MAPK and phosphatidylinositol 3 kinase ( PI 3 kinase ) activation . ^^^ Intracellular domain deleted p 185 ( neu ) receptors ( T691stop neu ) were able to associate with full length EGFR , but induced antagonistic effects on EGF dependent EGF receptor down regulation , cell proliferation , and activation of MAPK and PI 3 kinase pathways . ^^^ Ectodomain deleted p 185 ( neu ) proteins ( TDelta 5 ) were unable to physically associate with EGFR , and extracellular domain deleted p 185 ( neu ) forms failed to augment activation of MAPK and PI 3 kinase in response to EGF . ^^^ Association of EGFR with a carboxyl terminally truncated p 185 ( neu ) mutant ( TAPstop ) form did not increase transforming efficiency and phosphotyrosine content of the TAPstop species , and proliferation of EGFR . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In this study we compared the expression of several proteins ( p 53 , Rb , cyclin D 1 myc , bcl 2 , EGFR , neu , E Cadherin , Ep CAM , Desmoplakin 1 and nm 23 ) in the three major sites of HNSCC ( larynx , pharynx , and oral cavity ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Neu differentiation factors ( NDFs ) , or neuregulins , are epidermal growth factor like growth factors which bind to two tyrosine kinase receptors , ErbB 3 and ErbB 4 . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Three types of data have been collected : ( 1 ) clinical characteristics : age , sex , Karnofsky performance status , weight loss , T stage , and N stage ; ( 2 ) histopathology studies : histological types , tumor differentiation , status of vascular and lymphatic vessel invasions ; ( 3 ) laboratory measurements by immunohistochemistry assay : oncoprotein overexpression , including pan ras , c myc , neu , epidermal growth factor receptor ( EGFR ) and p 53 , and tumor cell proliferation by proliferating cell nuclear antigen ( PCNA ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Consistent with the notion that transforming erbB complexes induce sustained and unregulated MAPK activities , coexpression of p 185 ( neu ) and EGFR proteins to levels sufficient to transform murine fibroblasts also resulted in prolonged EGF induced ERK in vitro kinase activation . ^^^ Transforming erbB complexes , including EGFR homodimers , deltaEGFR homodimers , and p 185 ( neu ) / EGFR heterodimers , appear to induce sustained , unattenuated activation of MAPK activities that may contribute to increased transformation and resistance to apoptosis in primary human glioblastoma cells . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Using rat GEC in culture , we demonstrated that sublytic C5b 9 induced tyrosine phosphorylation of the epidermal growth factor receptor ( EGF R ) , Neu , fibroblast growth factor receptor 2 , and hepatocyte growth factor receptor . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
The aim of this study was to investigate the expression of neu / c erbB 2 oncoprotein , epidermal growth factor receptor ( EGFR ) , cathepsin D ( catD ) , progesterone receptor ( PR ) and tumor associated glycoprotein 72 ( TAG 72 ) in gastric carcinoma of these histological types . ^^^ RESULTS : Neu , EGFR , catD and TAG 72 concentrations were higher in the tumoral group ( p = 0 . 02 , p = 0 . 00001 , p = 0 . 002 and p = 0 . 007 , respectively ) . ^^^ No significant differences in EGFR and neu concentrations were seen between the two histological types . ^^^ Gastric carcinoma : expression of c erbB 2 / neu oncoprotein , epidermal growth factor receptor , cathepsin D , progesterone receptor and tumor associated glycoprotein 72 in different histological types . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Here we report that blockade of the epidermal growth factor receptor ( EGFR ) kinase with AG 1478 markedly delays breast tumor formation in mouse mammary tumor virus ( MMTV ) / Neu + MMTV / transforming growth factor alpha bigenic mice . ^^^ This delay was associated with inhibition of EGFR and Neu signaling , reduction of cyclin dependent kinase 2 ( Cdk 2 ) and mitogen activated protein kinase ( MAPK ) activities and cyclin D 1 , and an increase in the levels of the Cdk inhibitor p 27 ( Kip 1 ) . ^^^ Blockade of the epidermal growth factor receptor tyrosine kinase suppresses tumorigenesis in MMTV / Neu + MMTV / TGF alpha bigenic mice . ^^^ Overexpression of ErbB 2 / Neu has been causally associated with mammary epithelial transformation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
METHODS : We compared postnatal expression of four genes : neu and epidermal growth factor receptor genes ( EGFR ) , androgen upregulated in the ventral prostate of adult rats ( C 3 ) , and androgen repressed ( CK 8 ) in Sprague Dawley rats . ^^^ RESULTS : Growth factor receptors including neu and EGFR may be coordinately regulated in the basal cell population during prostate development . ^^^ Both neu and EGFR may be involved in androgen independent growth of basal cell population in prostate . ^^^ Differential expression of c erb B2 / neu , epidermal growth factor receptor , cytokeratin 8 , and the prostatic steroid binding protein gene in rat ventral prostate during postnatal development . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Modulation of EGFR and neu expression by n 6 and n 9 high fat diets in experimental mammary adenocarcinomas . ^^^ In this study we have investigated the influence of dietary mono and polyunsaturated lipids on 7 , 12 dimethylbenz ( alpha ) anthracene ( DMBA ) induced mammary tumorigenesis , and the modulation of expression of c erbB1 / EGFR and c erbB2 / neu as a mechanism of this influence . ^^^ On the other hand , two transcripts of EGFR and one neu mRNA were detected by chemiluminescent Northern blot in mammary adenocarcinomas . ^^^ High fat olive oil diet increased EGFR mRNA levels , specially those from 2 . 7 kb , and decreased the relative abundance of neu mRNA . ^^^ These data suggest that the modulating effect of dietary lipids on mammary carcinogenesis could result in changes of EGFR and neu mRNA , leading to an increase of EGFR activity by high fat corn oil diet and a decrease of EGFR and Neu signal transduction pathway by high fat olive oil diet . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
In the former , p 185 ( c neu ) expression and activation are controlled by EGF addition to the culture medium and by epidermal growth factor receptor ( EGFR ) activity , whereas the latter express unchangingly high levels of constitutively activated p 185 ( neu ) . ^^^ Interestingly , EGFR levels also vary and , analogously to phosphorylated p 185 ( c neu ) , the increase of EGFR content consequent to the [ D ] PDMP and EGF addition is reversed by exogenous GM ( 3 ) . ^^^ These findings indicate that changes in GM ( 3 ) content modulate the tyrosine phosphorylated p 185 ( c neu ) levels in a reversible manner , but this is not specific for p 185 ( c neu ) because EGFR levels are also modified . ^^^ Furthermore , these data suggest that GM ( 3 ) may play a functional role by affecting the internalisation pathway of p 185 ( c neu ) / EGFR heterodimers , but not of p 185 ( neu ) homodimers . . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Patients with urothelial carcinomas showing HER 2 / neu ( human epidermal growth factor receptor 2 ) overexpression are candidates for such a specific treatment ( trastuzumab ) . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Cell growth and apoptosis were examined in several NSCLC lines that express varying amounts of ERbeta , EGFR , and Neu but no full length ERalpha . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Moreover , transient Erk1 / 2 activation and BSMC proliferation were both dependent on epidermal growth factor receptor ( EGFR / HER1 ) but not neu receptor ( HER2 / ERB2 ) autophosphorylation . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Our previous work showed that , compared with parental U87MG human glioblastoma cells , vascular endothelial growth factor ( VEGF ) mRNA levels are decreased in U87 / T691 , a derivative line in which epidermal growth factor receptor ( EGFR ) signaling is inhibited by introduction of a truncated p 185 ( Neu ) protein ( A . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
Activated Neu expression in the midline glia suppressed apoptosis , similar to that seen with activated Drosophila EGF R expression . ^^^
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
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Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA
Interacting proteins: P04626 and P00533	Pubmed	SVM Score :0.0
NA