Signaling for Integrin α5/β1 Expression in Helicobacter pylori-Infected Gastric Epithelial AGS Cells

Authors: CHO, SOON OK1; KIM, KYUNG HWAN1; YOON, JOO-HEON2; KIM, HYEYOUNG3

Source: Annals of the New York Academy of Sciences, Volume 1090, Number 1, December 2006 , pp. 298-304(7)

Publisher: Wiley-Blackwell

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Abstract:

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Integrin expression in cancer tissues demonstrates its possible contribution to tumor progression, invasion, and metastasis. Helicobacter pylori (H. pylori) infection is related to gastric cancer and gastric inflammation. H. pylori induced upregulation in expression of integrin in gastric epithelia cells. Reactive oxygen species (ROS) are considered as an important regulator in the pathogenesis of H. pylori-induced gastric ulceration and carcinogenesis. Integrin expression may be regulated by oxidant-sensitive transcription factors, nuclear factor-κB (NF-κB) and activator protein-1 (AP-1). The present study aims to investigate whether H. pylori in a Korean isolate (HP99) induces the expression of integrin α5 and integrin β1, and whether H. pylori-induced expression of integrin α5 and integrin β1 are inhibited in the cells transfected with mutant genes for Ras (ras N-17), c-Jun (TAM-67), and IκBα(MAD-3) or treated with DPI, an inhibitor of NADPH oxidase. As a result, H. pylori induced the expression of integrin α5 and integrin β1 in gastric adenocarcinoma (AGS) cells time-dependently. Treatment of DPI or transfection with mutant genes for Ras (ras N-17), c-jun (TAM67), and IκBα(MAD3) inhibited H. pylori-induced expression of integrin α5 and integrin β1 in AGS cells. In conclusion, H. pylori activates Ras, NF-κB, and AP-1 and thus induces the expression of integrin α5 and integrin β1 in gastric epithelial cells. Inhibition of ROS production by DPI suppressed the expression of integrin α5 and integrin β1 in gastric epithelial cells. The results suggest the possible involvement of NADPH oxidase for ROS production in H. pylori-infected gastric epithelial cells.

Keywords: Helicobacter pylori; integrin α5/β1; AGS cells

Document Type: Research article

DOI: http://dx.doi.org/10.1196/annals.1378.032

Affiliations: 1: Department of Pharmacology and Institute of Gastroenterology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea 2: Department of Otorhinolaryngology and Biomolecule Secretion Research Center, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120752, Korea 3: Department of Food and Nutrition and Biomolecule Secretion Research Center, Brain Korea 21 Project, Yonsei University College of Human Ecology, Seoul 120-749, Korea

Publication date: 2006-12-01

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