Helicobacter pylori infection triggers aberrant expression of activation-induced cytidine deaminase in gastric epithelium (Nat Med, 2007, 13:470-476)

報告日期: 2007/10/30
報告時間: 17:10/18:00
報告學生: 鄧喬方
講評老師: 何漣漪

Helicobacter pylori infection triggers aberrant expression of activation-induced cytidine deaminase in gastric epithelium


Nature Medicine 13, 470-476 (2007)


Speaker: 鄧喬方

Commentator: 何漣漪 教授

Date: 2007/10/30, PM 5:10-6:00

Place: room 602



Infection with Helicobacter pylori (H. pylori) is a risk factor for the development of gastric cancer. However, the mechanisms by which H. pylori infection increases the risk of gastric cancer development are unknown. Activation-induced cytidine deaminase (AID), a member of the cytidine-deaminase family that acts as an editor of DNA and RNA, is an enzyme essential for somatic hypermutation and class-switch recombination in immunoglobulin genes. Many studies have shown that inappropriate expression of AID acts as a genomic mutator that contributes to tumorigenesis. Indeed, the authors found that some AID-transgenic mice developed gastric microadenoma. In this study, the authors first detected the AID expression level in AGS human gastric epithelial cells infected by H. pylori. The results of quantitative real-time RT-PCR, western blotting and immunostaining showed that infection with ‘cag’ pathogenicity island (cagPAI)-positive H. pylori induced aberrant AID expression in human gastric epithelial cells. Next, they also found that inhibiting IKK-dependent NF-kB activation reduced the induction of AID expression by cagPAI-positive H. pylori infection. That is, cagPAI-positive H. pylori infection induced aberrant AID expression via the IKK-dependent NF-kB activation pathway. Furthermore, they investigated the relationship between AID expression and TP53 mutations by the conditional AID expression system and AID siRNA. The data showed that H. pylori-mediated upregulation of AID resulted in the accumulation of somatic mutations in the TP53 tumor suppressor gene in human gastric epithelial cells. The consistent results were observed in the H. pylori-positive human gastric tissues. In conclusion, these findings provided evidence that aberrant AID expression caused by H. pylori infection might be a mechanism of mutation accumulation in the gastric mucosa during H. pylori-associated gastric carcinogenesis.



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