TRPV6 channel controls prostate cancer cell proliferation via Ca2+/NFAT-dependent pathways
TRPV6 channel controls prostate cancer cell proliferation via Ca2+/NFAT-dependent pathways
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DOI：
10.1038/sj.onc.1210545
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发表时间：
2007-11-15
期刊：
影响因子：
8
通讯作者：
Prevarskaya, N.
中科院分区：
文献类型：
--
作者：
Lehen'kyi, V.;Flourakis, M.;Prevarskaya, N.
瞬时受体电位通道，亚家族V，成员6（TRPV 6），在晚期前列腺癌中强烈表达，并且与Gleason > 7分级显著相关，在健康和良性前列腺组织中检测不到。然而，TRPV 6作为一个高度Ca 2+选择性通道在前列腺癌发生中的作用仍然知之甚少。在这里，我们报告TRPV 6是直接参与前列腺癌细胞（LNCaP细胞系）增殖的控制，通过降低：（i）增殖率;（ii）细胞积累在细胞周期的S期和（iii）增殖细胞核抗原（PCNA）的表达。我们证明，到LNCaP细胞的Ca 2+摄取是由TRPV 6介导的，与随后的下游活化的核因子的活化的T细胞转录因子（NFAT）。TRPV 6介导的Ca 2+内流也参与LNCaP细胞的凋亡抵抗。我们的研究结果表明，TRPV 6在LNCaP细胞的表达调节雄激素受体，但是，在配体非依赖性的方式。我们的结论是TRPV 6钙通道在前列腺癌细胞中的上调可能代表了维持较高增殖率，增加细胞存活和凋亡抗性的机制。
The transient receptor potential channel, subfamily V, member 6 (TRPV6), is strongly expressed in advanced prostate cancer and significantly correlates with the Gleason > 7 grading, being undetectable in healthy and benign prostate tissues. However, the role of TRPV6 as a highly Ca2+-selective channel in prostate carcinogenesis remains poorly understood. Here, we report that TRPV6 is directly involved in the control of prostate cancer cell (LNCaP cell line) proliferation by decreasing: (i) proliferation rate; (ii) cell accumulation in the S-phase of cell cycle and (iii) proliferating cell nuclear antigen (PCNA) expression. We demonstrate that the Ca2+ uptake into LNCaP cells is mediated by TRPV6, with the subsequent downstream activation of the nuclear factor of activated T-cell transcription factor (NFAT). TRPV6-mediated Ca2+ entry is also involved in apoptosis resistance of LNCaP cells. Our results suggest that TRPV6 expression in LNCaP cells is regulated by androgen receptor, however, in a ligand-independent manner. We conclude that the upregulation of TRPV6 Ca2+ channel in prostate cancer cells may represent a mechanism for maintaining a higher proliferation rate, increasing cell survival and apoptosis resistance as well.