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Induction of epidermal hyperplasia, hyperkeratosis, and papillomas in transgenic mice by a targeted v‐Ha‐ ras oncogene
Author(s) -
Greenhalgh David A.,
Rothnagel Joseph A.,
Quintanilla Maria I.,
Orengo Christine C.,
Gagne Todd A.,
Bundman Donnie S.,
Longley Mary A.,
Roop Dennis R.
Publication year - 1993
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.2940070208
Subject(s) - biology , transgene , carcinogenesis , genetically modified mouse , oncogene , phenotype , epidermis (zoology) , hyperplasia , cancer research , hyperkeratosis , keratin , microbiology and biotechnology , gene , genetics , endocrinology , cell cycle , anatomy
The regulatory elements of the human keratin K1 gene have been used to target expression of the v‐Ha‐ ras oncogene exclusively in the epidermis of transgenic mice. We developed 12 transgenic mouse lines that express the HK1. ras transgene, producing epidermal hyperplasia in neonates and hyperkeratosis in juveniles. Eventually this skin phenotype diminished but with time adult animals developed papillomas that could persist or regress. The rate and frequency of tumorigenesis appeared to be limited, which suggests that v‐Ha‐ ras requires a second or even third event to elicit and maintain a benign phenotype in transgenic mice. Since in certain transgenic lines papillomas appeared at wound sites, it appears that the promotion stimulus from wounding may be a second event. We envision that such transgenic mice that express v‐Ha‐ ras in the epidermis will become a powerful model for assessing how environmental and molecular factors affect the process of multistage skin carcinogenesis in vivo, as well as a model for evaluating novel therapeutic protocols.