Loss of growth control by TGF-beta occurs at a late stage of mouse skin carcinogenesis and is independent of ras gene activation

Oncogene. 1991 Aug;6(8):1465-70.


The relationship between the expression of a mutant ras gene in epithelial cells and loss of responsiveness to the negative effects of transforming growth factor beta (TGF-beta) is presently unclear. We have investigated this question using a series of cell lines derived from benign and malignant mouse skin tumours which express mutant forms of the H-ras gene. Immortalised, non-tumorigenic mouse epidermal cells respond to TGF-beta by cessation of growth, whereas in a series of malignant carcinoma lines the response was substantially reduced. Introduction of a mutant H-ras gene into the immortalised cells did not lead to any appreciable change in TGF-beta responsiveness, suggesting that initiation of carcinogenesis by ras mutation does not directly alter growth control by this pathway. Of two non-tumorigenic papilloma lines tested which had mutant H-ras genes, one retained complete sensitivity to TGF-beta, whereas the other showed a similar response to carcinomas. We conclude that growth control by TGF-beta is lost at a relatively late stage of carcinogenesis in this system, and is independent of ras gene activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Division / drug effects
  • Cell Division / physiology
  • Cell Transformation, Neoplastic / drug effects*
  • Cell Transformation, Neoplastic / pathology
  • DNA, Neoplasm / metabolism
  • Epithelium / pathology
  • Epithelium / physiopathology
  • Gene Expression Regulation, Neoplastic / physiology*
  • Genes, ras / genetics*
  • Mice
  • Mutation / genetics
  • Skin Neoplasms / pathology*
  • Skin Neoplasms / physiopathology
  • Thymidine / metabolism
  • Transcriptional Activation
  • Transforming Growth Factor beta / physiology*
  • Tritium
  • Tumor Cells, Cultured


  • DNA, Neoplasm
  • Transforming Growth Factor beta
  • Tritium
  • Thymidine