Association between diversity in the Src homology 2 domain-containing tyrosine phosphatase binding site of Helicobacter pylori CagA protein and gastric atrophy and cancer
Association between diversity in the Src homology 2 domain-containing tyrosine phosphatase binding site of Helicobacter pylori CagA protein and gastric atrophy and cancer
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DOI：
10.1086/381782
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发表时间：
2004-03-01
影响因子：
6.4
通讯作者：
Hatakeyama, M
中科院分区：
文献类型：
--
作者：
Azuma, T;Yamazaki, S;Hatakeyama, M
我们研究了幽门螺杆菌CagA蛋白的多样性与临床预后的关系。对115株临床分离株的cagA基因进行了序列测定。体外感染检测CagA与含酪氨酸磷酸酶(SHP-2)的Src同源2结构域的结合亲和力。观察到两种主要的CagA亚型：东亚型和西方型。感染东亚CagA阳性菌株的胃炎患者的炎症分级、胃炎活动性和萎缩程度显著高于感染cagA阴性或西方CagA阳性菌株的胃炎患者。所有从胃癌患者中分离的菌株均为东亚CagA阳性。东亚CagA具有比西方CagA更强的SHP-2结合活性。这些结果提示，东亚CagA阳性幽门螺杆菌感染与萎缩性胃炎和胃癌有关，东亚CagA阳性菌株诱导的持续性活动性炎症可能在疾病的发病机制中发挥作用。
We investigated the relationship between the diversity of Helicobacter pylori CagA protein and clinical outcome. The cagA gene was sequenced in 115 clinical isolates. The binding affinity of CagA to Src homology 2 domain containing tyrosine phosphatase (SHP-2) was examined by in vitro infection. Two major CagA subtypes were observed - the East Asian and the Western type. The grades of inflammation, activity of gastritis, and atrophy were significantly higher in patients with gastritis infected with the East Asian CagA-positive strain than in patients with gastritis infected with cagA-negative or Western CagA-positive strains. All strains isolated from patients with gastric cancer were East Asian CagA positive. East Asian CagA exhibited stronger SHP-2-binding activity than did Western CagA. These findings suggest that infection with East Asian CagA - positive H. pylori is associated with atrophic gastritis and gastric cancer and that persistent active inflammation induced by the East Asian CagA- positive strain may play a role in the pathogenesis of disease.