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膜联蛋白 A4:一种利用蛋白质组学方法研究幽门螺杆菌感染的胃癌新型分子标志物。

Annexin A4: A novel molecular marker for gastric cancer with Helicobacter pylori infection using proteomics approach.

机构信息

Institute of Molecular and Cellular Biology, National Taiwan University, Taipei, Taiwan.

出版信息

Proteomics Clin Appl. 2008 Apr;2(4):619-34. doi: 10.1002/prca.200780088. Epub 2008 Mar 7.

Abstract

Helicobacter pylori was reported to be an important risk factor for the carcinogenesis of gastric cancer. Here, we used a proteomic approach to find differentially expressed proteins between the normal and tumor tissue of gastric cancer patients infected with H. pylori. In our results, we found annexin A4 was over-expressed in patients infected with H. pylori and was found in tumor cells, and over-expressed in gastric cancer SCM-1 cells after H. pylori infection. Ca(2+ ) can be induced by H. pylori and interact with annexin A4 Ca(2+) binding site to block the calmodulin-activated chloride conductance activation; therefore, it produces a new environment that benefits the malignant existence of H. pylori and raises the risk for gastric cancer. We also found interleuken-8 (IL-8) expression levels were increased in H. pylori infected SCM-1 cells. Combined with previous reports and our results, we summarize that the over-expression of annexin A4 in SCM-1 cells with H. pylori infection may subsequently induce IL-8 which can further cause tumor angiogenesis. In this paper, we show that annexin A4 is a potential novel molecular marker for gastric cancer with H. pylori infection, and our results may provide a new insight in the development of new anti-cancer drugs.

摘要

幽门螺杆菌被报道为胃癌发生的重要危险因素。在这里,我们使用蛋白质组学方法来寻找感染幽门螺杆菌的胃癌患者正常组织和肿瘤组织之间差异表达的蛋白质。在我们的结果中,我们发现 annexin A4 在感染幽门螺杆菌的患者中过度表达,并且存在于肿瘤细胞中,并且在幽门螺杆菌感染后胃癌 SCM-1 细胞中过度表达。Ca(2+) 可以被幽门螺杆菌诱导,并与 annexin A4 Ca(2+) 结合位点相互作用,从而阻断钙调蛋白激活的氯离子电导的激活;因此,它产生了有利于幽门螺杆菌恶性存在的新环境,并增加了胃癌的风险。我们还发现白细胞介素-8 (IL-8) 在感染幽门螺杆菌的 SCM-1 细胞中的表达水平增加。结合以前的报告和我们的结果,我们总结出在感染幽门螺杆菌的 SCM-1 细胞中 annexin A4 的过度表达可能随后诱导 IL-8,这可以进一步导致肿瘤血管生成。在本文中,我们表明 annexin A4 是一种潜在的与幽门螺杆菌感染相关的胃癌新型分子标志物,我们的结果可能为开发新的抗癌药物提供新的见解。

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