Journal Article

Induction of melanoma in TPras transgenic mice

Marianne Broome Powell, Paul R. Gause, Paul Hyman, Jacalyn Gregus, Maria Lluria-Prevatt, Ray Nagle and G. Tim Bowden

in Carcinogenesis

Volume 20, issue 9, pages 1747-1753
Published in print September 1999 | ISSN: 0143-3334
Published online September 1999 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/20.9.1747
Induction of melanoma in TPras transgenic mice

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In order to study the oncogenesis of melanocytes, transgenic mouse lines were established that express a mutated human Ha-ras (TPras) gene in pigment producing cells. The ras transgenic mice exhibit an altered phenotype, including melanocytic hyperplasia and a muted agouti coat, indicative of hyperproliferative melanocytes. These mice and their wild-type littermates have been subjected to a variety of carcinogenesis protocols, including 7,12-dimethylbenz-[a]anthracene (DMBA), 12-O-tetradecanoylphorbol-13-acetate (TPA) and UV radiation exposure. Topical DMBA treatment of TPras mice resulted in a high incidence of melanomas. Metastatic lesions were observed in skin, lungs and lymph nodes. TPA treatment of TPras mice induced a small number of papillomas but no nevi or melanomas. UV light exposures induced papillomas in negative littermate and melanomas in some albino TPras mice. These results show that melanocytes expressing an activated Ha-ras in the TPras transgenic mice are susceptible to induction of melanoma by DMBA.

Keywords: DMBA, 7,12-dimethylbenz[a]anthracene; SCID, severe combined immunodeficient; TPA, 12-O-tetradecanoylphorbol-13-acetate.

Journal Article.  5439 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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