Affiliation:
1. McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison, Wisconsin 53706
Abstract
ABSTRACT
High-risk human papillomaviruses (HPVs) are the causative agents of certain human cancers. HPV type 16 (HPV16) is the papillomavirus most frequently associated with cervical cancer in women. The E6 and E7 genes of HPV are expressed in cells derived from these cancers and can transform cells in tissue culture. Animal experiments have demonstrated that E6 and E7 together cause tumors. We showed previously that E6 and E7 together or E7 alone could induce skin tumors in mice when these genes were expressed in the basal epithelia of the skin. In this study, we investigated the role that the E6 gene plays in carcinogenesis. We generated K14E6 transgenic mice, in which the HPV16 E6 gene was directed in its expression by the human keratin 14 promoter (hK14) to the basal layer of the epidermis. We found that E6 induced cellular hyperproliferation and epidermal hyperplasia and caused skin tumors in adult mice. Interestingly, the tumors derived from E6 were mostly malignant, as opposed to the tumors from E7 mice, which were mostly benign. This result leads us to hypothesize that E6 may contribute differently than E7 to HPV-associated carcinogenesis; whereas E7 primarily contributes to the early stages of carcinogenesis that lead to the formation of benign tumors, E6 primarily contributes to the late stages of carcinogenesis that lead to malignancy.
Publisher
American Society for Microbiology
Subject
Virology,Insect Science,Immunology,Microbiology
Reference56 articles.
1. ras gene mutations and HPV infection are common in human laryngeal carcinoma;Anwar K.;Int. J. Cancer,1993
2. Neuroepithelial carcinomas in mice transgenic with human papillomavirus type 16 E6/E7 ORFs;Arbeit J. M.;Am. J. Pathol.,1993
3. Loss of p53 protein in human papillomavirus type 16 E6-immortalized human mammary epithelial cells
4. Identification of human papillomavirus type 18 transforming genes in immortalized and primary cells.
5. E7 protein of human papilloma virus-16 induces degradation of retinoblastoma protein through the ubiquitin-proteasome pathway;Boyer S. N.;Cancer Res.,1996
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