E-cadherin Gene Promoter Hypermethylation in H. pylori-Induced Enlarged Fold Gastritis


Reprint request to: Yoko Murayama, MD, PhD, Department of Gastroenterology and Hepatology, Itami City Hospital, 1-100, Koyaike, Itami, 664-8540, Japan. Tel.: +81-72-777-3773; Fax: +81-72-781-9888; E-mail: yokom@imed2.med.osaka-u.ac.jp or murayama@hosp.itami.hyogo.jp


Background:  Promoter hypermethylation of E-cadherin plays an important role on gastric carcinogenesis. We have previously reported that the odds ratio for gastric carcinoma and the prevalence of diffuse-type early gastric carcinoma in Helicobacter pylori-induced enlarged fold gastritis increased with increasing fold width. Thus, we examined E-cadherin methylation in gastric mucosa from H. pylori-induced enlarged fold gastritis before and after H. pylori eradication. Moreover, we analyzed the mechanism of H. pylori infection-induced E-cadherin hypermethylation.

Materials and methods:  Twenty-three H. pylori-positive patients with enlarged folds, 18 H. pylori-positive and seven H. pylori-negative patients without enlarged folds, were involved in the study. E-cadherin promoter methylation was studied using quantitative methylation-specific polymerase chain reaction. We investigated methylation percentage and DNA methyltransferase activity in gastric cancer cell lines treated with EGF, TNFα, and MG132.

Results: E-cadherin methylation percentage of the gastric antral and body mucosa in H. pylori-positive patients with enlarged folds was much greater than that in both H. pylori-positive and -negative patients without enlarged folds. After H. pylori eradication, the methylation percentage in six patients with enlarged fold gastritis decreased significantly from 15.6 ± 3.9 to 8.8 ± 2.2 (p < .05). Moreover, the methylation was induced by TNFα, MG132, and EGF treatment, and DNA methyltransferase activity was induced by EGF treatment in MKN-1 cells.

Conclusions:  Our findings suggest that the hypermethylation of E-cadherin promoter might be involved in the process of gastric carcinoma through the specialized factors in H. pylori-induced enlarged fold gastritis.