Transgenic Overexpression of Transforming Growth Factor α Bypasses the Need for c-Ha-ras Mutations in Mouse Skin Tumorigenesis
| Autor: | Robert Vassar, Elaine Fuchs, M E Hutton |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
Genetically modified mouse
TGF alpha Skin Neoplasms Transgene Molecular Sequence Data Mice Transgenic Biology medicine.disease_cause Mice medicine Animals Molecular Biology Mutation Base Sequence Papilloma integumentary system Cell growth Gene Amplification DNA Neoplasm Cell Biology Transforming Growth Factor alpha Gene Expression Regulation Neoplastic Disease Models Animal Genes ras Tetradecanoylphorbol Acetate Immunology Cancer research Wounds and Injuries Carcinogenesis Research Article Transforming growth factor |
| Zdroj: | Molecular and Cellular Biology. 12:4643-4653 |
| ISSN: | 1098-5549 |
| DOI: | 10.1128/mcb.12.10.4643-4653.1992 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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