BACKGROUND: Helicobacter pylori infection increases the risk of gastric carcinogenesis. The aim of the present study was to determine whether H. pylori could up-regulate the expression of the epidermal growth factor receptor (EGFR), a critical gene in the carcinogenic process. METHODS: AGS gastric epithelial cells were infected with cag(+) toxigenic or cag(-) nontoxigenic strains of H. pylori or isogenic mutants. EGFR protein expression was determined by Western blotting and immunofluorescence. EGFR mRNA levels were evaluated using real-time polymerase chain reaction. The signaling pathways leading to EGFR up-regulation were examined using the ERK1/2 inhibitor PD98059, the Src inhibitor pp2, the nuclear factor- kappa B inhibitor caffeic acid phenethyl ester, EGFR neutralizing antibodies, and the EGFR kinase inhibitor AG1478. RESULTS: Infection of AGS cells by H. pylori significantly increased EGFR mRNA and protein levels. We found that this effect was limited to cag(+) H. pylori strains and that mutants with a defective type IV secretion system were unable to cause EGFR up-regulation. Increased EGFR expression was found to be dependent on EGFR receptor transactivation, ERK1/2 phosphorylation, and Src activation. CONCLUSION: Infection of gastric epithelial cells by H. pylori triggers an autocrine loop whereby EGFR transactivation leads to the up-regulation of EGFR expression. This, in turn, may contribute to unrestrained epithelial cell proliferation and carcinogenesis.
BACKGROUND:Helicobacter pylori infection increases the risk of gastric carcinogenesis. The aim of the present study was to determine whether H. pylori could up-regulate the expression of the epidermal growth factor receptor (EGFR), a critical gene in the carcinogenic process. METHODS: AGS gastric epithelial cells were infected with cag(+) toxigenic or cag(-) nontoxigenic strains of H. pylori or isogenic mutants. EGFR protein expression was determined by Western blotting and immunofluorescence. EGFR mRNA levels were evaluated using real-time polymerase chain reaction. The signaling pathways leading to EGFR up-regulation were examined using the ERK1/2 inhibitor PD98059, the Src inhibitor pp2, the nuclear factor- kappa B inhibitor caffeic acid phenethyl ester, EGFR neutralizing antibodies, and the EGFR kinase inhibitor AG1478. RESULTS: Infection of AGS cells by H. pylori significantly increased EGFR mRNA and protein levels. We found that this effect was limited to cag(+) H. pylori strains and that mutants with a defective type IV secretion system were unable to cause EGFR up-regulation. Increased EGFR expression was found to be dependent on EGFR receptor transactivation, ERK1/2 phosphorylation, and Src activation. CONCLUSION: Infection of gastric epithelial cells by H. pylori triggers an autocrine loop whereby EGFR transactivation leads to the up-regulation of EGFR expression. This, in turn, may contribute to unrestrained epithelial cell proliferation and carcinogenesis.
Authors: Alain P Gobert; Mohammad Asim; M Blanca Piazuelo; Thomas Verriere; Brooks P Scull; Thibaut de Sablet; Ashley Glumac; Nuruddeen D Lewis; Pelayo Correa; Richard M Peek; Rupesh Chaturvedi; Keith T Wilson Journal: J Immunol Date: 2011-10-10 Impact factor: 5.422
Authors: Johanna C Sierra; Stuart Hobbs; Rupesh Chaturvedi; Fang Yan; Keith T Wilson; Richard M Peek; D Brent Polk Journal: Am J Physiol Gastrointest Liver Physiol Date: 2013-05-16 Impact factor: 4.052
Authors: Lida Q Fuentes; Carlos E Reyes; José M Sarmiento; Carolina I Villanueva; Carlos D Figueroa; Javier Navarro; Carlos B González Journal: Cell Signal Date: 2008-05-25 Impact factor: 4.315
Authors: Fang Yan; Hanwei Cao; Rupesh Chaturvedi; Uma Krishna; Stuart S Hobbs; Peter J Dempsey; Richard M Peek; Timothy L Cover; M Kay Washington; Keith T Wilson; D Brent Polk Journal: Gastroenterology Date: 2009-01-01 Impact factor: 22.682