Induction of melanoma in TPras transgenic mice

Carcinogenesis. 1999 Sep;20(9):1747-53. doi: 10.1093/carcin/20.9.1747.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene
  • Albinism
  • Animals
  • Carcinoma / chemically induced
  • Carcinoma / genetics
  • Gene Expression Regulation
  • Genes, ras*
  • Genetic Predisposition to Disease
  • Hair Color / genetics
  • Hyperplasia
  • Melanocytes / drug effects
  • Melanocytes / pathology
  • Melanoma / chemically induced
  • Melanoma / etiology
  • Melanoma / genetics*
  • Melanoma / pathology
  • Mice
  • Mice, SCID
  • Mice, Transgenic
  • Monophenol Monooxygenase / genetics
  • Neoplasm Metastasis
  • Neoplasms, Radiation-Induced / chemically induced
  • Neoplasms, Radiation-Induced / etiology
  • Neoplasms, Radiation-Induced / genetics
  • Neoplasms, Radiation-Induced / pathology
  • Papilloma / chemically induced
  • Papilloma / etiology
  • Papilloma / genetics
  • Papilloma / pathology
  • Promoter Regions, Genetic
  • Skin Neoplasms / chemically induced
  • Skin Neoplasms / etiology
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology
  • Skin Pigmentation / genetics
  • Tetradecanoylphorbol Acetate
  • Ultraviolet Rays

Substances

  • 9,10-Dimethyl-1,2-benzanthracene
  • Monophenol Monooxygenase
  • Tetradecanoylphorbol Acetate