TY - JOUR
T1 - Induction of melanoma in TPras transgenic mice
AU - Powell, Marianne Broome
AU - Gause, Paul R.
AU - Hyman, Paul
AU - Gregus, Jacalyn
AU - Lluria-Prevatt, Maria
AU - Nagle, Ray
AU - Bowden, G. Tim
N1 - Funding Information:
The authors would like to thank Drs Allan Balmain and Ken Brown for their assistance in developing the TPras mice. This work was supported in part by National Institutes of Health grants CA 27502 and 5P30CA23074, and by generous gifts from the Jane Cuzner Charitable Lead Trust and ‘The Phoenix Friends’ to the Arizona Cancer Center. The paper’s contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. P.R.G. was supported in part by National Science Foundation Experiences for Undergraduates in Molecular Biosciences grant BIR9423290.
PY - 1999
Y1 - 1999
N2 - 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[α]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.
AB - 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[α]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.
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U2 - 10.1093/carcin/20.9.1747
DO - 10.1093/carcin/20.9.1747
M3 - Article
C2 - 10469620
AN - SCOPUS:0242471456
SN - 0143-3334
VL - 20
SP - 1747
EP - 1753
JO - Carcinogenesis
JF - Carcinogenesis
IS - 9
ER -