E-cadherin Gene Promoter Hypermethylation in H. pylori-Induced Enlarged Fold Gastritis
Article first published online: 21 AUG 2007
Volume 12, Issue 5, pages 523–531, October 2007
How to Cite
Miyazaki, T., Murayama, Y., Shinomura, Y., Yamamoto, T., Watabe, K., Tsutsui, S., Kiyohara, T., Tamura, S. and Hayashi, N. (2007), E-cadherin Gene Promoter Hypermethylation in H. pylori-Induced Enlarged Fold Gastritis. Helicobacter, 12: 523–531. doi: 10.1111/j.1523-5378.2007.00519.x
- Issue published online: 21 AUG 2007
- Article first published online: 21 AUG 2007
- Helicobacter pylori;
- quantitative MSP;
- enlarged fold gastritis
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.