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Updated: Aug 18, 2026

Cell Population Analyses During Skin Carcinogenesis
Published on: August 21, 2013
Transgenic overexpression of transforming growth factor alpha bypasses the need for c-Ha-ras mutations in mouse skin
R Vassar1, M E Hutton, E Fuchs
1Department of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute, University of Chicago, Illinois 60637.
Abstract:
The induction of skin papillomas in mice can be divided into two different stages. Chemical initiation frequently elicits mutations in the Ha-ras gene, leading to the constitutive activation of ras. The second step, promotion, involves repetitive topical application of phorbol esters or wounding, leading to epidermal hyperproliferation and papilloma formation. We have found that overexpression of transforming growth factor alpha (TGF-alpha) in the basal epidermal layer of transgenic mice yielded papillomas directly upon wounding or 12-O-tetradecanoylphorbol-13-acetate treatment without the need for an initiator. Moreover, papillomas from TGF-alpha mice did not exhibit mutations in the Ha-ras gene. Interestingly, TGF-alpha acted synergistically with 12-O-tetradecanoylphorbol-13-acetate to enhance epidermal hyperproliferation. Our results demonstrate a central role for TGF-alpha overexpression in tumorigenesis and provide an important animal model for the study of skin tumorigenesis.
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