| INK4A , CDC 6 , and MCM 5 : predictive biomarkers in cervical preinvasive neoplasia and cervical cancer . ^^^ AIM : To analyse and compare expression patterns of three potential biomarkers p 16 ( INK4A ) , CDC 6 , and MCM 5 and evaluate their use as predictive biomarkers in squamous and glandular cervical preinvasive neoplasia . ^^^ METHODS : Immunocytochemical analysis of p 16 ( INK4A ) , MCM 5 , and CDC 6 expression was performed on 20 normal , 38 cervical intraepithelial neoplasia 1 ( CIN 1 ) , 33 CIN 2 , 46 CIN 3 , 10 squamous cell carcinoma , 19 cervical glandular intraepithelial neoplasia ( cGIN ) , and 10 adenocarcinoma samples . ^^^ Staining intensity was assessed using a 0 3 scoring system . p 16 ( INK4A ) , MCM 5 , and CDC 6 expression was also examined in ThinPrep slides exhibiting mild , moderate , and severe dyskaryosis . ^^^ CDC 6 may be a biomarker of high grade and invasive lesions of the cervix , with limited use in low grade dysplasia . p 16 ( INK4A ) was the most reliable marker of cervical dysplasia . ^^^ |
| Furthermore , human lung carcinomas with high levels of Cdc 6 are associated with low levels of p 16 ( INK4a ) . ^^^ Oncogenic activity of Cdc 6 through repression of the INK4 / ARF locus . ^^^ Here we have identified a putative DNA replication origin at the INK4 / ARF locus that assembles a multiprotein complex containing Cdc 6 , Orc 2 and MCMs , and that coincides with a conserved noncoding DNA element ( regulatory domain RD ( INK4 / ARF ) ) . ^^^ We have found that high levels of Cdc 6 result in RD ( INK4 / ARF ) dependent transcriptional repression , recruitment of histone deacetylases and heterochromatinization of the INK4 / ARF locus , and a concomitant decrease in the expression of the three tumour suppressors encoded by this locus . ^^^ Consistent with its ability to repress the INK4 / ARF locus , Cdc 6 has cellular immortalization activity and neoplastic transformation capacity in cooperation with oncogenic Ras . ^^^ |