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[慢性炎症与胃癌的发生]

[Chronic inflammation and gastric cancer development].

作者信息

Chiba Tsutomu, Marusawa Hiroyuki, Matsumoto Yuko, Takai Atsushi

机构信息

Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University.

出版信息

Nihon Rinsho. 2012 Oct;70(10):1694-8.

Abstract

H. pylori-induced gastritis plays important roles in gastric cacrcinogenesis and cancer development is characterized by accumulation of various gene aberrations. Activation-induced cytidine deaminase (AID) is exclusively expressed in B lymphocytes and is essential for diversification of immunoglobulin genes. H. pylori-positive human gastritis mucosa ectopically express AID. H. pylori infection to gastric cells in vitro induced AID in association with induction of various gene mutations and deletions. H. pylori-induced AID is mediated by NFkappaB. Furthermore, AID gene introduction into gastric mucosal cells accelerated p53 gene mutations, and inhibition of AID using siRNA significantly reduced H. pylori-induced p53 gene mutations. Thus, H. pylori infection induces ectopic AID expression in the gastric mucosal cells via NFkappaB activation, resulting in various gene mutations and aberrations in the gastric mucosal cells leading to gastric cancer development.

摘要

幽门螺杆菌诱导的胃炎在胃癌发生过程中起重要作用,癌症发展的特征是各种基因畸变的积累。激活诱导的胞苷脱氨酶(AID)仅在B淋巴细胞中表达,对免疫球蛋白基因的多样化至关重要。幽门螺杆菌阳性的人类胃炎黏膜中异位表达AID。体外幽门螺杆菌感染胃细胞可诱导AID表达,并伴有各种基因突变和缺失。幽门螺杆菌诱导的AID由核因子κB介导。此外,将AID基因导入胃黏膜细胞可加速p53基因突变,使用小干扰RNA抑制AID可显著降低幽门螺杆菌诱导的p53基因突变。因此,幽门螺杆菌感染通过激活核因子κB诱导胃黏膜细胞中AID异位表达,导致胃黏膜细胞发生各种基因突变和畸变,从而引发胃癌。

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