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幽门螺杆菌导致胃腺癌患者胃上皮细胞中CagA酪氨酸磷酸化。

CagA tyrosine phosphorylation in gastric epithelial cells caused by Helicobacter pylori in patients with gastric adenocarcinoma.

作者信息

Lai Yo-Ping, Yang Jyh-Chin, Lin Tzu-Zung, Wang Jin-Town, Lin Jaw-Town

机构信息

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.

出版信息

Helicobacter. 2003 Jun;8(3):235-43. doi: 10.1046/j.1523-5378.2003.00148.x.

DOI:10.1046/j.1523-5378.2003.00148.x
PMID:12752736
Abstract

BACKGROUND

Tyrosine phosphorylation of Helicobacter pylori cytotoxin-associated protein of in gastric epithelial cells is reported. The goals of this study are first to examine the occurrence of CagA tyrosine phosphorylation in H. pylori strains isolated from patients with gastric adenocarcinoma and gastritis, and second to clarify the relationship between the diversity of tyrosine phosphorylation motifs and the presence of CagA tyrosine phosphorylation.

METHODS

Fifty-eight clinical isolates of H. pylori from patients with gastric adenocarcinoma (29 cases) and gastritis (29 cases) were studied for CagA tyrosine phosphorylation by Western blotting. Sequence diversity of tyrosine phosphorylation motifs was analysed among positive- or negative-CagA tyrosine phosphorylation isolates.

RESULTS

Positive CagA tyrosine phosphorylation was found in 93.1% (27 of 29) of strains from gastric adenocarcinoma patients and 51.7% (15 of 29) of strains from gastritis patients (p < 0.001). Intact motifs were found in H. pylori isolates with CagA tyrosine phosphorylation. Of the 16 negative CagA tyrosine phosphorylation isolates, intact tyrosine phosphorylation motifs were found in 15 isolates.

CONCLUSIONS

CagA tyrosine phosphorylation, which is significantly greater in strains from gastric adenocarcinoma patients, may play a role in gastric carcinogenesis, and could be a better marker of more virulent strains than the cag pathogenicity island in Asia, where the cag pathogenicity island is present in nearly all H. pylori strains. Sequence diversity of tyrosine phosphorylation motifs on CagA was not related to the presence of tyrosine phosphorylation. The absence of tyrosine phosphorylation motif might result in negative tyrosine phosphorylation phenotypes, but such motifs are not the sole factors associated with CagA tyrosine phosphorylation.

摘要

背景

有报道称胃上皮细胞中幽门螺杆菌细胞毒素相关蛋白存在酪氨酸磷酸化。本研究的目的,一是检测从胃腺癌患者和胃炎患者中分离出的幽门螺杆菌菌株中CagA酪氨酸磷酸化的发生情况,二是阐明酪氨酸磷酸化基序多样性与CagA酪氨酸磷酸化存在之间的关系。

方法

采用蛋白质免疫印迹法研究了58株从胃腺癌患者(29例)和胃炎患者(29例)中分离出的幽门螺杆菌临床分离株的CagA酪氨酸磷酸化情况。分析了CagA酪氨酸磷酸化阳性或阴性分离株中酪氨酸磷酸化基序的序列多样性。

结果

胃腺癌患者菌株中93.1%(29株中的27株)存在CagA酪氨酸磷酸化阳性,胃炎患者菌株中51.7%(29株中的15株)存在CagA酪氨酸磷酸化阳性(p<0.001)。在具有CagA酪氨酸磷酸化的幽门螺杆菌分离株中发现了完整的基序。在16株CagA酪氨酸磷酸化阴性分离株中,有15株发现了完整的酪氨酸磷酸化基序。

结论

CagA酪氨酸磷酸化在胃腺癌患者的菌株中显著更高,可能在胃癌发生中起作用,并且在亚洲可能是比cag致病岛更好的高毒力菌株标志物,在亚洲几乎所有幽门螺杆菌菌株都存在cag致病岛。CagA上酪氨酸磷酸化基序的序列多样性与酪氨酸磷酸化的存在无关。酪氨酸磷酸化基序的缺失可能导致酪氨酸磷酸化表型阴性,但这些基序不是与CagA酪氨酸磷酸化相关的唯一因素。

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