HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hung, K.-H. Articles by Sheu, B.-S. Search for Related Content PubMed PubMed Citation Articles by Hung, K.-H. Articles by Sheu, B.-S. Agricola Articles by Hung, K.-H. Articles by Sheu, B.-S.

Host Wnt/β-catenin pathway triggered by Helicobacter pylori correlates with regression of gastric intestinal metaplasia after H. pylori eradication

¹ Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC

² Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC

³ Department of Pathology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC

⁴ Department of Pathology, Ton-Yen General Hospital, Hsinchu, Taiwan, ROC

⁵ Institute of Clinical Pharmacy, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC

⁶ Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC

⁷ Department of Internal Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC

Correspondence
Bor-Shyang Sheu
sheubs{at}mail.ncku.edu.tw

Received October 15, 2008
Accepted January 7, 2009

Helicobacter pylori eradication can reverse gastric intestinal metaplasia (IM) in some but not all patients. H. pylori induces high levels of nuclear β-catenin staining in IM tissues, as well as overexpression of cyclooxygenase-2 (COX-2). This study investigated whether the Wnt/β-catenin pathway plays a role in IM regression following H. pylori eradication. Sixty-five H. pylori-infected patients with IM who had achieved successful H. pylori eradication provided paired gastric samples before and after eradication to analyse the persistence of IM, and to assess COX-2 and nuclear β-catenin expression. The host genotypes of single nucleotide polymorphisms (SNPs) of the COX-2, β-catenin (CTNNB1) and adenomatous polyposis coli (APC) genes were analysed. In addition, expression of β-catenin, E-cadherin and phosphorylated and unphosphorylated glycogen synthase kinase 3β (GSK-3β) in cell lines challenged with H. pylori isolates from patients with and without IM persistence was compared by immunoanalysis. After a mean 33.9-month follow-up after H. pylori eradication, 44 patients (67.7 %) with IM persistence had a higher rate of high-level nuclear β-catenin expression in IM tissue than those without IM persistence (P=0.008). The patients with IM persistence had a higher rate of AA, GG and AA APC SNP genotypes at positions 4479, 5268 and 5465, respectively, than the patients without IM persistence (P=0.022). The H. pylori isolates from the patients with IM regression after H. pylori eradication induced more phospho-GSK-3β in AGS cells than isolates from patients with IM persistence (P=0.011). It is likely that interactions with H. pylori and the patient's Wnt/β-catenin genetic predisposition determine the outcome of IM persistence following H. pylori eradication.

Abbreviations: CI, confidence interval; COX-2, cyclooxygenase-2; GSK-3β, glycogen synthase kinase 3β; IM, intestinal metaplasia; SNP, single nucleotide polymorphism.