Kim Myoung Ok, Kim Sung Hyun, Shin Mi Jung, Yu Dong Hoon, Kim Bong Soo, Chang Kyu Tae, Lee Sanggyu, Park Yong Bok, Lee Tae-Hoon, Ryoo Zae Young
School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu, 702-701, Korea.
Oncol Res. 2007;16(7):325-32. doi: 10.3727/000000006783980964.
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.
人乳头瘤病毒16型（HPV16）是子宫颈癌发生发展的主要致病因素。我们研究了E6/E7在肿瘤形成中的作用。在二甲基苯并[a]蒽（DMBA）启动及12-O-十四酰佛波醇-13-乙酸酯（TPA）促进的两阶段皮肤致癌过程中，皮肤特异性E6/E7转基因小鼠的肿瘤数量约为非转基因小鼠的两倍。该模型显示转基因小鼠的表皮细胞增殖显著增加。8-羟基-2'-脱氧鸟苷（8OH-dG）检测试验表明，TPA处理后转基因小鼠的氧化性DNA损伤显著更高。在DMBA/TPA两阶段诱导致癌模型中，皮肤中E6/E7的过表达加剧了肿瘤形成的发生率。HPV16 E6/E7似乎作为一种致癌增强因子，需要DMBA启动及TPA促进。
