title: 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.
authors.affiliation: School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu, 702-701, Korea.
authors.forename: Myoung Ok
authors.initials: MO
authors.lastname: Kim
authors.forename: Sung Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Mi Jung
authors.initials: MJ
authors.lastname: Shin
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Yu
authors.forename: Bong Soo
authors.initials: BS
authors.lastname: Kim
authors.forename: Kyu Tae
authors.initials: KT
authors.lastname: Chang
authors.forename: Sanggyu
authors.initials: S
authors.lastname: Lee
authors.forename: Yong Bok
authors.initials: YB
authors.lastname: Park
authors.forename: Tae-Hoon
authors.initials: TH
authors.lastname: Lee
authors.forename: Zae Young
authors.initials: ZY
authors.lastname: Ryoo
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000818:Animals; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D020405:Dermis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009856:Oncogene Proteins, Viral / Q000032:analysis / Q000235:genetics*; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins / Q000032:analysis / Q000235:genetics*; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D015127:9,10-Dimethyl-1,2-benzanthracene; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D013755:Tetradecanoylphorbol Acetate