Skin Hyperproliferation and Susceptibility to Chemical Carcinogenesis in Transgenic Mice Expressing E6 and E7 of Human Papillomavirus Type 38

• DOI: 10.1128/jvi.79.23.14899-14908.2005
• Publication Date: 2005-11-10T18:12:58Z
• Authors: Wen Dong; Ulrich Kloz; Rosita Accardi; Sandra Caldeira; Wei-Min Tong; Zhao-Qi Wang; Lars Jansen; Matthias Dürst; Bakary S. Sylla; Lutz Gissmann; Massimo Tommasino
• Keywords: Epidermis (zoology); Keratin 14

The oncoproteins E6 and E7 of human papillomavirus type 38 (HPV38) display several transforming activities in vitro, including immortalization primary keratinocytes. To evaluate the oncogenic viral proteins an vivo model, we generated transgenic mice expressing HPV38 under control bovine homologue keratin 10 (K10) promoter. Two distinct lines E6/E7-expressing that express genes at different levels were obtained. In both lines, induced cellular proliferation, hyperplasia, dysplasia epidermis. rate occurrence these events was proportional to expression two lines. Exposure epidermis nontransgenic UV led p21WAF1 accumulation cell cycle arrest. contrast, keratinocytes from continued proliferate not positive for p21WAF1, indicating checkpoints are altered genes. Although did develop spontaneous tumors during their life span, two-stage carcinogen treatment a high incidence papillomas, keratoacanthomas, squamous-cell carcinomas compared with animals. Together, data show properties vivo, providing further support role carcinogenesis.