title: Tyrosine kinase and MAPK inhibition of TNF-alpha- and EGF-stimulated IEC-6 cell growth.
abstract: 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.
authors.affiliation: Department of Pediatrics, Ste-Justine Hospital, Montreal, Quebec, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Dionne
authors.forename: I D
authors.initials: ID
authors.lastname: D'Agata
authors.forename: F M
authors.initials: FM
authors.lastname: Ruemmele
authors.forename: E
authors.initials: E
authors.lastname: Levy
authors.forename: J
authors.initials: J
authors.lastname: St-Louis
authors.forename: A K
authors.initials: AK
authors.lastname: Srivastava
authors.forename: D
authors.initials: D
authors.lastname: Levesque
authors.forename: E G
authors.initials: EG
authors.lastname: Seidman
mesh_terms: D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005419:Flavonoids / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D007583:Jejunum / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D005419:Flavonoids; D047428:Protein Kinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D004815:Epidermal Growth Factor; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one