Pathophysiological functions of chloride intracellular channel protein 3 (CLIC3) in human gastric cancer have been unclear. In the tissue microarray analysis using 107 gastric cancer specimens, CLIC3 expression was negatively correlated with pathological tumor depth, and the patients with lower expression of CLIC3 exhibited poorer prognosis. CLIC3 was expressed in the plasma membrane of cancer cells in the tissue. CLIC3 expression was also found in a human gastric cancer cell line (MKN7). In whole-cell patch-clamp recordings of the cells expressing CLIC3, NPPB-sensitive outwardly rectifying Cl- currents were observed. Cell proliferation was significantly accelerated by knockdown of CLIC3 in MKN7 cells. On the other hand, the proliferation was attenuated by exogenous CLIC3 expression in human gastric cancer cells (KATOIII and NUGC-4) in which endogenous CLIC3 expression is negligible. Our results suggest that CLIC3 functions as a Cl- channel in the plasma membrane of gastric cancer cells and that decreased expression of CLIC3 results in unfavorable prognosis of gastric cancer patients.

中文翻译：

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CLIC3氯化物通道在人胃癌细胞中的病理生理特性。

尚不清楚氯化物细胞内通道蛋白3（CLIC3）在人胃癌中的病理生理功能。在使用107例胃癌组织进行的组织芯片分析中，CLIC3表达与病理性肿瘤深度呈负相关，而CLIC3表达较低的患者预后较差。CLIC3在组织中癌细胞的质膜中表达。在人胃癌细胞系（MKN7）中也发现CLIC3表达。在表达CLIC3的细胞的全细胞膜片钳记录中，观察到NPPB敏感的向外整流的Cl-电流。MKN7细胞中的CLIC3敲低显着促进了细胞增殖。另一方面，在人胃癌细胞（KATOIII和NUGC-4）中外源CLIC3表达减弱了增殖，其中内源CLIC3表达可以忽略。我们的结果表明，CLIC3在胃癌细胞的质膜中充当Cl-通道，而CLIC3的表达降低会导致胃癌患者的预后不良。