Introduction of a Ha-ras oncogene into rat liver epithelial cells and parenchymal hepatocytes confers resistance to the growth inhibitory effects of TGF-beta

Oncogene. 1989 Jan;4(1):19-25.


Growth of rat liver epithelial cells (RLEC) and primary cultures of parenchymal hepatocytes is potently inhibited by TGF-beta. Transfection of a mutated Ha-ras oncogene, but not a human c-myc oncogene, into RLEC resulted in cell lines resistant to growth inhibition by TGF-beta under anchorage-dependent conditions. Infection of primary rat hepatocyte cultures with v-Ha-ras yielded a cell line likewise insensitive to inhibition by TGF-beta. Binding of [125I]TGF-beta to Ha-ras-transfected RLEC was reduced relative to control or c-myc-transfected cells. These data suggest that activation of a Ha-ras oncogene in epithelial cells may result in escape from negative growth control and hence be a critical step during carcinogenesis. However, although Ha-ras induced resistance to growth inhibition by TGF-beta under anchorage-dependent conditions, TGF-beta inhibited the spontaneous growth in soft agar of all cell lines containing the Ha-ras oncogene. This may reflect an alteration in regulation of extracellular matrix proteins and related enzymes responsible for anchorage-independent growth.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Adhesion
  • Cell Line
  • Cell Transformation, Neoplastic
  • DNA / biosynthesis
  • Epithelial Cells
  • Epithelium / ultrastructure
  • Humans
  • Liver / cytology
  • Liver / ultrastructure
  • Oncogene Protein p21(ras)
  • Oncogene Proteins, Viral / metabolism
  • Oncogenes*
  • Rats
  • Transfection*
  • Transforming Growth Factors / antagonists & inhibitors*
  • Transforming Growth Factors / metabolism


  • Oncogene Proteins, Viral
  • Transforming Growth Factors
  • DNA
  • Oncogene Protein p21(ras)