DMBA/TPA-induced tumor formation is aggravated in human papillomavirus type 16 E6/E7 transgenic mouse skin

Abstract

Human papillomavirus type 16 (HPV16) is a major causative factor in the development of uterine cervical carcinomas. We investigated the role of E6/E7 in tumor formation. Skin-specific E6/E7 transgenic mice showed approximately twice as many tumors compared with nontransgenic mice in dimethylbenz[a]anthracene (DMBA)-initiated and a 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted two-stage skin carcinogenesis. This model showed a significant increase of epidermal cell proliferation in the transgenic mice. The 8-hydroxy-2'deoxyguanosine (8OH-dG) detection assay showed that oxidative DNA damage was significantly higher in the transgenic mice after TPA treatments. The overexpression of E6/E7 in the skin in the DMBA/TPA two-stage-induced carcinogenesis model aggravated the incidence of tumor formation. HPV16 E6/E7 appears to act as an enhancer of carcinogenesis that requires initiation by DMBA and promotion by TPA.