Overexpression of H-ras oncogene induces resistance to the growth-inhibitory action of transforming growth factor beta-1 (TGF-beta 1) and alters the number and type of TGF-beta 1 receptors in rat intestinal epithelial cell clones

Oncogene. 1992 Mar;7(3):521-6.

Abstract

In this report, we utilize rat intestinal cell (IEC-18) clones expressing an activated human H-ras gene to investigate the relationship between malignant transformation and growth control by transforming growth factor beta (TGF-beta). We demonstrate that clones expressing high levels of H-ras oncogene lose sensitivity to the growth inhibitory action of TGF-beta. The loss of sensitivity is related to the degree of H-ras expression and is shown to be a direct consequence of H-ras expression through the use of a clonal cell line with inducible expression of activated H-ras. Co-incident with the loss of growth inhibition, ras-expressing clones display an altered expression of TGF-beta-binding proteins as detectable by [125I]TGF-beta cross-linking. While IEC-18 cells express type II (92 kDa) binding protein predominantly, H-ras expression induces a shift to predominantly type I (69 kDa) binding protein expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Division
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Clone Cells
  • Gene Expression
  • Genes, ras*
  • Growth Inhibitors
  • In Vitro Techniques
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / metabolism*
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Rats
  • Receptors, Cell Surface / physiology*
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta / pharmacology*

Substances

  • Growth Inhibitors
  • Receptors, Cell Surface
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta
  • Proto-Oncogene Proteins p21(ras)