The Role of Tumour Supressors and Viral onOncoproteins in Cervical Carcinogenesis

Overview

This article summarizes current knowledge of the cervical carcinogenesis with a special focus onthe molecular mechanisms involving the interaction of celullar tumour supressors (p53, RB, p73)with viral oncoproteins (E6, E7). The E6-induced degradation of p53 protein results in the inhibi-tion of apoptosis, inability to repair DNA and fixation of mutations. The p53-dependent tumouri-genesis is influenced by interaction not only with E6/HPV 16, 18 but also with MDM2, bcl-2 and RBprotein. The polymorphism of p53 seems to contribute to malignant transformation of cervix. Oncontrary, there are experimental data showing that p53 may not be the only factor playing role inmalignant transformation in cervical cancer. It has been generally agreed that viral oncoproteinE6 is a critical step in the onset of malignant transformation of cervix. There is a vast number ofexperimental and clinical studies confirming the validity of E6 induced cervical cancer includingalteration of the genotype and phenotypic characteristics of the transforming cells. The moderntools of molecular biology offer an exact diagnosis as well as relevant targets for gene therapy ofthe cervical cancer.

Key words:
viral oncoproteins, tumour supressors, malignant transformation, cervical neoplasia