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Tyrosine Kinase and MAPK Inhibition of TNF-α- and EGF-Stimulated IEC-6 Cell Growth

https://doi.org/10.1006/bbrc.1997.7922Get rights and content

Abstract

The role of TNF-α in modulating intestinal crypt cell growth was examined, in comparison with EGF. Both significantly increased IEC-6 cell proliferation. Neither EGF nor TNF-α 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-α stimulation. TNF-α increased ERK1 and ERK2 MAPK phosphorylation. A MAPK assay confirmed the increased activity upon TNF-α stimulation. Selective inhibition of MAPK activation by PD98059 resulted in a dose dependent inhibition of TNF-α or EGF-induced IEC-6 cell growth. These findings suggest a role for TNF-α in the regulation of intestinal epithelial cell growth and that the mitogenic effect of TNF-α requires protein tyrosine phosphorylation and MAPK activation.

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