Helicobacter pyloriActivates the Early Growth Response 1 Protein in Gastric Epithelial Cells

Open Access
Publisher Website
Google Scholar
Abstract
The early growth response 1 (Egr-1) transcription factor is rapidly induced by various stimuli and is implicated in the regulation of cell growth, differentiation, and gene expression. The aim of this study was to examine the effect ofHelicobacter pylorion the expression of Egr-1 and Egr-1-regulated genes in gastric epithelial AGS cells. Egr-1 expression was assayed by immunoblotting and electrophoretic mobility shift assays usingH. pylori-stimulated AGS cells. Transient transfection experiments with promoter-reporter constructs of CD44, ICAM-1, and CD95L were used for expression studies.H. pyloriinduced the expression of Egr-1 in gastric epithelial cell lines in a dose-dependent manner, with the rapid kinetics that are typical of this class of transcription factors. Immunohistochemical studies of biopsies revealed that Egr-1 expression is more abundant inH. pylori-positive patients than in uninfected individuals. Reporter-promoter transfection studies indicated that Egr-1 binding is required for theH. pylori-induced transcriptional promoter activity of the CD44, ICAM-1, and CD95L (APO-1/Fas) constructs. The blocking ofegr-1with an antisense sequence preventedH. pylori-induced Egr-1 and CD44 protein expression. The MEK1/2 signaling cascade participates inH. pylori-mediated Egr-1 expression, but the p38 pathway does not. The data indicate thatH. pyloriinduces Egr-1 expression in AGS cells in vitro and that the Egr-1 protein is readily detectable in biopsies fromH. pylori-positive subjects. These observations suggest thatH. pylori-associated Egr-1 expression may play a role, in part, inH. pylori-induced pathology.

This publication has 52 references indexed in Scilit: