EPIDERMAL CANCER-ASSOCIATED WITH EXPRESSION OF HUMAN PAPILLOMAVIRUS TYPE-16 E6-ONCOGENES AND E7-ONCOGENES IN THE SKIN OF TRANSGENIC MICE

Certain ''high-risk'' anogenital human papillomaviruses (HPVs) have be en associated with the majority of human cervical carcinomas. In these cancers, two papillomaviral genes, E6 and E7, are commonly expressed. In this study we provide evidence that expression of the E6 and E7 ge nes from the high-risk HPV-16 in the skin of transgenic mice potentiat ed the development of preneoplastic lesions, and a high percentage of these epidermal lesions subsequently developed into locally invasive c ancers. High levels of E6/E7 expression were found in these tumors rel ative to the preneoplastic lesions, and expression was localized to th e proliferating, poorly differentiated epidermal cells. Also, the p53 and Rb genes were found to be intact, not mutationally inactivated, in representative skin tumors. These findings demonstrate that the E6 an d E7 genes from a papillomavirus etiologically associated with human c ervical cancer can contribute to the development of epidermal cancers in an animal model.