DMBA/TPA-induced tumor formation is aggravated in human papillomavirus type 16 E6/E7 transgenic mouse skin.
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.
Kim
Myoung Ok
MO
School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu, 702-701, Korea.
Kim
Sung Hyun
SH
Shin
Mi Jung
MJ
Yu
Dong Hoon
DH
Kim
Bong Soo
BS
Chang
Kyu Tae
KT
Lee
Sanggyu
S
Park
Yong Bok
YB
Lee
Tae-Hoon
TH
Ryoo
Zae Young
ZY
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*
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