Schwarz Eva C, Wissenbach Ulrich, Niemeyer Barbara A, Strauss Bettina, Philipp Stephan E, Flockerzi Veit, Hoth Markus
Department of Physiology, University of the Saarland, Homburg, Germany.
Cell Calcium. 2006 Feb;39(2):163-73. doi: 10.1016/j.ceca.2005.10.006. Epub 2005 Dec 13.
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.
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。