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瞬时受体电位香草酸亚型6(TRPV6)增强钙依赖性细胞增殖。

TRPV6 potentiates calcium-dependent cell proliferation.

作者信息

Schwarz Eva C, Wissenbach Ulrich, Niemeyer Barbara A, Strauss Bettina, Philipp Stephan E, Flockerzi Veit, Hoth Markus

机构信息

Department of Physiology, University of the Saarland, Homburg, Germany.

出版信息

Cell Calcium. 2006 Feb;39(2):163-73. doi: 10.1016/j.ceca.2005.10.006. Epub 2005 Dec 13.

Abstract

The Ca(2+) homeostasis within cells controls a diversity of cellular processes including gene transcription, proliferation and apoptosis. Perturbance of Ca(2+) signaling may induce deregulation of cell proliferation and suppression of cell death providing the basis for cancer development. In human prostate cancer, a correlation between the mRNA expression of the Ca(2+) channel TRPV6 and the staging of the cancer has been described. We have analyzed the influence of TRPV6 on cell proliferation within HEK-293 cells. We show that TRPV6 increases cell proliferation of HEK-293 cells in a Ca(2+) dependent manner. The increased proliferation correlates with slightly increased intracellular Ca(2+) levels without interfering with the intrinsic Ca(2+) dependence of HEK-293 cell proliferation. Low doses of econazole inhibit both, TRPV6 dependent Ca(2+) signals and cell proliferation while BTP2, a potent inhibitor of Ca(2+) signals and cell proliferation in T-cells, neither influences TRPV6 dependent Ca(2+) signals nor cell proliferation of HEK-293 cells. Our data demonstrate that TRPV6 increases the rate of Ca(2+) dependent cell proliferation which is a prerequisite for its potential role in tumor progression.

摘要

细胞内的钙离子稳态控制着多种细胞过程,包括基因转录、增殖和凋亡。钙离子信号的紊乱可能导致细胞增殖失调和细胞死亡受抑制,从而为癌症发展提供基础。在人类前列腺癌中,已报道钙离子通道TRPV6的mRNA表达与癌症分期之间存在相关性。我们分析了TRPV6对HEK-293细胞内细胞增殖的影响。我们发现TRPV6以钙离子依赖的方式增加HEK-293细胞的增殖。增殖增加与细胞内钙离子水平略有升高相关,且不干扰HEK-293细胞增殖的内在钙离子依赖性。低剂量的益康唑既能抑制TRPV6依赖的钙离子信号,也能抑制细胞增殖,而BTP2(一种T细胞中钙离子信号和细胞增殖的有效抑制剂)既不影响TRPV6依赖的钙离子信号,也不影响HEK-293细胞的增殖。我们的数据表明,TRPV6增加了钙离子依赖的细胞增殖速率,这是其在肿瘤进展中发挥潜在作用的前提条件。

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