Transgenic overexpression of transforming growth factor α bypasses the need for c-Ha-ras mutations in mouse skin tumorigenesis

Robert Vassar, M. Elizabeth Hutton, Elaine Fuchs

Research output: Contribution to journalArticle

99 Scopus citations

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 α (TGF-α) 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-α mice did not exhibit mutations in the Ha-ras gene. Interestingly, TGF-α acted synergistically with 12-O-tetradecanoylphorbol-13-acetate to enhance epidermal hyperproliferation. Our results demonstrate a central role for TGF-α overexpression in tumorigenesis and provide an important animal model for the study of skin tumorigenesis.

Original languageEnglish (US)
Pages (from-to)4643-4653
Number of pages11
JournalMolecular and cellular biology
Volume12
Issue number10
DOIs
StatePublished - Jan 1 1992

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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