Expression and significance of HERG protein in gastric cancer
Expression and significance of HERG protein in gastric cancer
复制标题
HERG蛋白在胃癌中的表达及意义
DOI：
10.4161/cbt.7.1.5126
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发表时间：
2008-01-01
影响因子：
3.6
通讯作者：
Fan, Dai-Ming
中科院分区：
文献类型：
--
作者：
Shao, Xiao-Dong;Wu, Kai-Chun;Fan, Dai-Ming
目的：我们前期的研究表明，人胃癌细胞中存在延迟整流钾电流，该电流与胃癌细胞的生长有关。编码延迟整流钾通道亚基的人乙醚相关基因（herg）已被证明参与肿瘤细胞的生长和死亡。本研究的目的是探讨胃癌组织和细胞中HERG蛋白的表达；分析HERG蛋白表达与胃癌患者临床病理特征的关系；探讨HERG蛋白对胃癌细胞生物学行为的影响。方法：采用免疫组织化学法和Western blot法分别检测胃癌组织和细胞中HERG蛋白的表达。通过siRNA技术对HERG蛋白进行还原。采用MTT法、克隆形成法、流式细胞术和细胞侵袭法评价胃癌细胞的增殖、克隆形成能力、细胞周期、凋亡和侵袭能力。采用裸鼠肿瘤生长观察胃癌细胞的致瘤性，膜片钳法记录HERG电流。结果：HERG蛋白在胃癌细胞中完全表达。HERG蛋白的表达与胃癌的分化、TNM分期及淋巴结受累有关。沉默HERG蛋白可以消除HERG电流，抑制胃癌细胞的增殖、克隆形成、侵袭性和致瘤性。降低HERG蛋白还能抑制胃癌细胞从G(1)期进入S期，诱导胃癌细胞凋亡。结论：HERG蛋白参与胃癌的发生，是胃癌潜在的治疗靶点。
Objectives: Our previous studies showed that delayed rectifier potassium currents existed in human gastric cancer cells and the currents were related to the growth of gastric cancer cells. Human ether-a-go-go-related gene (herg) encoding a subunit of delayed rectifier potassium channel has been indicated with involvement in tumor cell growth and death. The purpose of the present study is to investigate the expression of HERG protein in gastric cancer tissue and cells; analyze the relationship between the expression of HERG protein and the clinicopathological characteristics of patients with gastric cancer; explore the effects of HERG protein on biological behaviours of gastric cancer cells.Methods: The expression of HERG protein in gastric cancer tissues and cells was measured by immunohistochemistry and Western blot, respectively. Reduction of HERG protein was carried out by siRNA technology. The proliferation, ability of clone formation, cell cycle, apoptosis and invasive ability of gastric cancer cells were evaluated by MTT assay, clone formation assay, flow cytometry and cell invasion assay. Tumor growth in nude mice was to be used to access the tumorigenicity of gastric cancer cells and HERG currents were recorded by patch-clamp.Results: HERG protein was exclusively expressed in gastric cancer cells. The expression of HERG protein was associated with tumor differentiation, TNM stage and lymph node involvement of gastric cancer. Silencing HERG protein could eliminate the HERG currents and inhibit proliferation, clone formation, invasiveness and tumorigenicity of gastric cancer cells. Reducing HERG protein could also inhibit gastric cancer cells entering S phase from G(1) phase and induce apoptosis of gastric cancer cells.Conclusion: HERG protein is involved in carcinogenesis of gastric cancer and is a potential therapeutic target of gastric cancer.