Epidermal cancer associated with expression of human papillomavirus type 16 E6 and E7 oncogenes in the skin of transgenic mice.
Certain "high-risk" anogenital human papillomaviruses (HPVs) have been associated with the majority of human cervical carcinomas. In these cancers, two papillomaviral genes, E6 and E7, are commonly expressed. In this study we provide evidence that expression of the E6 and E7 genes from the high-risk HPV-16 in the skin of transgenic mice potentiated the development of preneoplastic lesions, and a high percentage of these epidermal lesions subsequently developed into locally invasive cancers. High levels of E6/E7 expression were found in these tumors relative to the preneoplastic lesions, and expression was localized to the proliferating, poorly differentiated epidermal cells. Also, the p53 and Rb genes were found to be intact, not mutationally inactivated, in representative skin tumors. These findings demonstrate that the E6 and E7 genes from a papillomavirus etiologically associated with human cervical cancer can contribute to the development of epidermal cancers in an animal model.
McArdle Laboratory for Cancer Research, University of Wisconsin, Madison 53706.
P F
PF
Lambert
H
H
Pan
H C
HC
Pitot
A
A
Liem
M
M
Jackson
A E
AE
Griep
D000818:Animals; D015139:Blotting, Southern; D003094:Collagen / Q000032:analysis / Q000096:biosynthesis; D005260:Female; D015870:Gene Expression; D016161:Genes, Retinoblastoma; D016158:Genes, p53; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis* / Q000235:genetics; D009857:Oncogenes; D027383:Papillomaviridae / Q000235:genetics*; D050725:Papillomavirus E7 Proteins; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D012097:Repressor Proteins; D012867:Skin / Q000382:microbiology / Q000473:pathology*; D012878:Skin Neoplasms / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000382:microbiology
C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D003094:Collagen