H Pylori
Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Oct 7, 2006; 12(37): 5972-5977
Published online Oct 7, 2006. doi: 10.3748/wjg.v12.i37.5972
H pylori stimulates proliferation of gastric cancer cells through activating mitogen-activated protein kinase cascade
Yong-Chang Chen, Ying Wang, Jing-Yan Li, Wen-Rong Xu, You-Li Zhang
Yong-Chang Chen, Ying Wang, Jing-Yan Li, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu Province, China
Wen-Rong Xu, School of Medical Technology, Jiangsu University, Zhenjiang, Jiangsu Province, China
You-Li Zhang, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, China
Supported by the National Natural Science Foundation of China, No. 30340036 and No. 30470891; Grant from Jiangsu University and Zhenjiang Key Institute of Clinical Laboratory Medicine (SH2006066)
Correspondence to: Yong-Chang Chen, School of Medicine, 2 Dongwu Road, Zhenjiang 212001, Jiangsu Province, China. ycchen54@ujs.edu.cn
Telephone: +86-511-2986558 Fax: +86-511-5038002
Received: May 28, 2006
Revised: June 12, 2006
Accepted: July 7, 2006
Published online: October 7, 2006

AIM: To explore the mechanism by which H pylori causes activation of gastric epithelial cells.

METHODS: A VacA (+) and CagA (+) standard H pylori line NCTC 11637 and a human gastric adenocarcinoma derived gastric epithelial cell line BGC-823 were applied in the study. MTT assay and 3H-TdR incorporation test were used to detect the proliferation of BGC-823 cells and Western blotting was used to detect the activity and existence of related proteins.

RESULTS: Incubation with H pylori extract increased the proliferation of gastric epithelial cells, reflected by both live cell number and DNA synthesis rate. The activity of extracellular signal-regulated protein kinase (ERK) signal transduction cascade increased within 20 min after incubation with H pylori extract and appeared to be a sustained event. MAPK/ERK kinase (MEK) inhibitor PD98059 abolished the action of H pylori extract on both ERK activity and cell proliferation. Incubation with H pylori extract increased c-Fos expression and SRE-dependent gene expression. H pylori extract caused phosphorylation of several proteins including a protein with molecular size of 97.4 kDa and tyrosine kinase inhibitor genistein inhibited the activation of ERK and the proliferation of cells caused by H pylori extract.

CONCLUSION: Biologically active elements in H pylori extract cause proliferation of gastric epithelial cells through activating tyrosine kinase and ERK signal transduction cascade.

Keywords: H pylori, Gastric cancer cells, Proliferation, Mitogen-activated protein kinase