Up-regulation of expression and lack of 5 CpG island hypermethylation of p16 INK4a in HPV-positive cervical carcinomas

摘要

BackgroundHigh risk type human papilloma viruses (HR-HPV) induce carcinomas of the uterine cervix by expressing viral oncogenes E6 and E7. Oncogene E7 of HR-HPV disrupts the pRb/E2F interaction, which negatively regulates the S phase entry. Expression of tumor suppressor p16^ink4a drastically increases in majority of HR-HPV associated carcinomas due to removal of pRb repression. The p16^ink4a overexpression is an indicator of an aberrant expression of viral oncogenes and may serve as a marker for early diagnostic of cervical cancer. On the other hand, in 25–57% of cervical carcinomas hypermethylation of the p16 INK4a promoter has been demonstrated using a methylation-specific PCR, MSP. To evaluate a potential usage of the p16 INK4a 5' CpG island hypermethylation as an indicator of tumor cell along with p16^ink4a overexpression, we analyzed the methylation status of p16 INK4a in cervical carcinomas