Ras, but not Src, transformation of RIE-1 epithelial cells is dependent on activation of the mitogen-activated protein kinase cascade

Oncogene. 1998 May;16(20):2565-73. doi: 10.1038/sj.onc.1201784.

Abstract

Src transformation of NIH3T3 mouse fibroblasts has been shown to be dependent on Ras function. Since we recently showed that the signaling pathways that mediate Ras transformation of RIE-1 rat intestinal epithelial cells are distinct from those that cause Ras transformation of fibroblasts, we utilized three approaches to determine if Src transformation of RIE-1 cells is dependent on Ras. First, although both Ras and Src cause upregulation of an epidermal growth factor (EGF) receptor-dependent autocrine growth loop, only Ras transformation required this activity. Second, whereas both Src and Ras caused upregulation of the p42 and p44 mitogen-activated protein kinases (MAPKs), only Ras transformation was blocked by the inhibition of MAPK activation by treatment with the PD 98059 MEK inhibitor. Third, treatment with the farnesyltransferase inhibitor FTI-277 blocked Ras, but not Src, transformation. Taken together, these observations suggest that Src transformation of RIE-1 cells is not dependent on Ras. Finally, we determined that Ras activation of Raf-independent pathways alone is sufficient to cause growth transformation of RIE-1 cells. Thus, both Ras and Src cause transformation of RIE-1 cells via pathways distinct from those required to cause transformation of NIH3T3 cells.

Publication types

  • 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

  • Alkyl and Aryl Transferases / antagonists & inhibitors
  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cell Transformation, Neoplastic*
  • Cells, Cultured
  • Enzyme Inhibitors / pharmacology
  • Epithelial Cells / pathology*
  • ErbB Receptors / metabolism
  • Farnesyltranstransferase
  • Genes, ras*
  • Genes, src*
  • Methionine / analogs & derivatives
  • Methionine / pharmacology
  • Mutation
  • Proto-Oncogene Proteins c-raf / metabolism
  • Rats
  • Up-Regulation

Substances

  • Enzyme Inhibitors
  • FTI 277
  • Methionine
  • Alkyl and Aryl Transferases
  • Farnesyltranstransferase
  • ErbB Receptors
  • Proto-Oncogene Proteins c-raf
  • Calcium-Calmodulin-Dependent Protein Kinases