E-cadherin gene promoter hypermethylation in H-Pylori-induced enlarged fold gastritis
E-cadherin gene promoter hypermethylation in H-Pylori-induced enlarged fold gastritis
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DOI：
10.1111/j.1523-5378.2007.00519.x
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发表时间：
2007-10-01
期刊：
影响因子：
4.4
通讯作者：
Hayashi, Norio
中科院分区：
文献类型：
--
作者：
Miyazaki, Tamana;Murayama, Yoko;Hayashi, Norio
背景：E-钙粘蛋白启动子高甲基化在胃癌发生中起重要作用。我们之前报道过，幽门螺杆菌引起的扩大皱襞性胃炎中胃癌的比值比和弥漫型早期胃癌的患病率随着皱襞宽度的增加而增加。因此，我们在幽门螺杆菌根除前后检测了幽门螺杆菌诱导的扩大皱襞性胃炎胃粘膜中的E-钙粘蛋白甲基化。此外，我们还分析了H. pylori感染引起E-cadherin高甲基化的机制。 材料与方法：23例H. pylori阳性且皱襞增大的患者、18例H. pylori阳性和7例H. pylori阴性但无皱襞增大的患者参与本研究。使用定量甲基化特异性聚合酶链反应研究了 E-钙粘蛋白启动子甲基化。我们研究了经EGF、TNFα和MG132处理的胃癌细胞系的甲基化百分比和DNA甲基转移酶活性。结果：幽门螺杆菌阳性且皱襞增大的患者胃窦和胃体粘膜的E-钙粘蛋白甲基化百分比远高于幽门螺杆菌阳性和阴性且无皱襞增大的患者。根除幽门螺杆菌后，六名肥厚型胃炎患者的甲基化百分比从 15.6 +/- 3.9 显着下降至 8.8 +/- 2.2 (p < .05)。此外，在MKN-1细胞中，TNFα、MG132和EGF处理可诱导甲基化，EGF处理可诱导DNA甲基转移酶活性。结论：我们的研究结果表明，E-cadherin启动子的高甲基化可能通过H. pylori诱导的肥大性胃炎的特殊因素参与胃癌的发生过程。
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, TNF alpha, 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 TNF alpha, 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.