Tyrosine kinase and MAPK inhibition of TNF-alpha- and EGF-stimulated IEC-6 cell growth

Biochem Biophys Res Commun. 1998 Jan 6;242(1):146-50. doi: 10.1006/bbrc.1997.7922.


The role of TNF-alpha in modulating intestinal crypt cell growth was examined, in comparison with EGF. Both significantly increased IEC-6 cell proliferation. Neither EGF nor TNF-alpha overcame the inhibitory effect on growth exerted by the tyrosine kinase inhibitor genistein. Immunoblots with phosphotyrosine antibodies showed increased tyrosine phosphorylation of IEC-6 cell proteins in response to EGF and TNF-alpha stimulation. TNF-alpha increased ERK1 and ERK2 MAPK phosphorylation. A MAPK assay confirmed the increased activity upon TNF-alpha stimulation. Selective inhibition of MAPK activation by PD98059 resulted in a dose dependent inhibition of TNF-alpha or EGF-induced IEC-6 cell growth. These findings suggest a role for TNF-alpha in the regulation of intestinal epithelial cell growth and that the mitogenic effect of TNF-alpha requires protein tyrosine phosphorylation and MAPK activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
  • Cell Division / drug effects
  • Cell Line
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Epidermal Growth Factor / pharmacology*
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Epithelial Cells / physiology
  • Flavonoids / pharmacology
  • Genistein / pharmacology
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / growth & development*
  • Jejunum / cytology
  • Jejunum / drug effects
  • Jejunum / growth & development*
  • Protein Kinase Inhibitors*
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Rats
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Flavonoids
  • Protein Kinase Inhibitors
  • Tumor Necrosis Factor-alpha
  • Epidermal Growth Factor
  • Genistein
  • Protein-Tyrosine Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one