Induction of melanoma in TPras transgenic mice

In order to study the oncogenesis of melanocytes, transgenic mouse lines we re established that express a mutated human Ha-ras (TPras) gene in pigment producing cells, The ras transgenic mice exhibit an altered phenotype, incl uding melanocytic hyperplasia and a muted agouti coat, indicative of hyperp roliferative melanocytes. These mice and their wild-type littermates have b een subjected to a variety of carcinogenesis protocols, including 7,12-dime thylbenz[a]anthracene (DMBA), 12-O-tetradecanoylphorbol-13-acetate (TPA) an d UV radiation exposure. Topical DMBA treatment of TPras mice resulted in a high incidence of melanomas, Metastatic lesions were observed in skin, lun gs and lymph nodes. TPA treatment of TPras mice induced a small number of p apillomas but no nevi or melanomas, UV light exposures induced papillomas i n negative littermate and melanomas in some albino TPras mice. These result s show that melanocytes expressing an activated Ha-ras in the TPras transge nic mice are susceptible to induction of melanoma by DMBA.