Protection against human papillomavirus type 16-E7 oncogene-induced tumorigenesis by in vivo expression of dominant-negative c-jun.
Expression of the human papillomavirus (HPV) type 16 E6 and E7 gene products is a risk factor for human cervical carcinogenesis as well as skin and oral carcinogenesis. Expression of the HPV-16 E7 gene in mouse skin induces hyperplasia and enhances tumor promotion. Expression of dominant-negative c-jun (TAM67) in the mouse skin protects mice from 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced papillomagenesis without blocking mitogen-induced hyperproliferation. To determine the role of activator protein-1 (AP-1) in HPV-induced cancer, we crossed HPV-16 E7 mice with TAM67 mice and analyzed the effects of DMBA/TPA on tumor promotion. We showed that expression of TAM67 protected mice from HPV-16 E7-enhanced tumorigenesis, suggesting AP-1 as a target for prevention of HPV-induced cancer.
Basic Research Laboratory, National Institute of Cancer-Frederick, Maryland, USA.
Matthew R
MR
Young
Linda
L
Farrell
Paul
P
Lambert
Parirokh
P
Awasthi
Nancy H
NH
Colburn
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D005799:Genes, Dominant; D016758:Genes, jun; D051379:Mice; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000235:genetics / Q000517:prevention & control*; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D027383:Papillomaviridae / Q000472:pathogenicity*; D050725:Papillomavirus E7 Proteins; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity
D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D015127:9,10-Dimethyl-1,2-benzanthracene; D013755:Tetradecanoylphorbol Acetate