E-cadherin gene promoter hypermethylation in H. pylori-induced 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.


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, TNFalpha, 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 TNFalpha, 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.
Miyazaki
Tamana
T
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, 2-2 K1, Yamadaoka, Suita 565-0871, Japan.
Murayama
Yoko
Y
Shinomura
Yasuhisa
Y
Yamamoto
Takahiro
T
Watabe
Kenji
K
Tsutsui
Shusaku
S
Kiyohara
Tatsuya
T
Tamura
Shinji
S
Hayashi
Norio
N
D000328:Adult; D000368:Aged; D001706:Biopsy; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D019175:DNA Methylation; D005260:Female; D005753:Gastric Mucosa / Q000382:microbiology / Q000473:pathology; D005756:Gastritis / Q000382:microbiology / Q000473:pathology*; D016481:Helicobacter Infections / Q000382:microbiology / Q000473:pathology / Q000503:physiopathology*; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000502:physiology*
D015820:Cadherins