Protein phosphatase 2A and the regulation of human papillomavirus gene activity.

Abstract

Oncogenic human papillomavirus (HPV) types are considered to be causally involved in the pathogenesis of cervical cancer (zur Hausen 1991a). DNA of the oncogenic HPV types has been detected in more than 90% of cervical carcinomas (zur Hausen 1989). HPV-16 and HPV-18 are the most common H PV types present in cervical carcinomas and their E6 and E7 genes are able to immortalize but not to oncogenically transform primary human keratinocytes (Pirisi et al. 1988; Woodworth et al. 1989). Proliferation of cervical carcinoma cell lines appears to be dependent on E6/E7 expression, indicating an important role of the E6 and E7 genes in the maintenance of the oncogenic phenotype of these cancer cells (von Knebel Doeberitz et al. 1991). Oncogenic conversion of HPV-16-and HPV-18-immortalized keratinocytes is probably dependent on specific host cell DNA modifications occuring only after a long time in in vitro cultivation (Hurlin et al. 1991; Pecoraro et al. 1991). A minority of cervical intra-epithelial neoplasias, causally associated with the same oncogenic HPV types as cervical cancer, develops into cancer after a long latency period of generally more than 10 years. This strongly suggests that the expression of the HPV E6/E7 genes is necessary but not sufficient for the maintenance of the malignant phenotype of cervical cancer cells (zur Hausen 1989; Vousden 1989).KeywordsOkadaic AcidSimian VirusHuman Foreskin KeratinocytesOncogenic PhenotypeMouse Skin Tumor PromoterThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.