Lehen'kyi V, Flourakis M, Skryma R, Prevarskaya N
Inserm, U-800, Equipe labellisée par la Ligue Nationale contre le cancer, Villeneuve d'Ascq, France.
Oncogene. 2007 Nov 15;26(52):7380-5. doi: 10.1038/sj.onc.1210545. Epub 2007 May 28.
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 Ca(2+)-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 Ca(2+) 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 Ca(2+) 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 Ca(2+) channel in prostate cancer cells may represent a mechanism for maintaining a higher proliferation rate, increasing cell survival and apoptosis resistance as well.
瞬时受体电位阳离子通道亚家族V成员6（TRPV6）在晚期前列腺癌中高表达，且与Gleason评分>7显著相关，在健康和良性前列腺组织中未检测到。然而，TRPV6作为一种高度Ca(2+)选择性通道在前列腺癌发生中的作用仍知之甚少。在此，我们报告TRPV6通过降低以下指标直接参与前列腺癌细胞（LNCaP细胞系）增殖的控制：（i）增殖率；（ii）细胞周期S期的细胞积累；（iii）增殖细胞核抗原（PCNA）的表达。我们证明LNCaP细胞对Ca(2+)的摄取由TRPV6介导，随后激活T细胞活化核因子转录因子（NFAT）的下游信号。TRPV6介导的Ca(2+)内流也参与LNCaP细胞的抗凋亡作用。我们的结果表明，LNCaP细胞中TRPV6的表达受雄激素受体调节，然而，是以非配体依赖的方式。我们得出结论，前列腺癌细胞中TRPV6 Ca(2+)通道的上调可能是维持较高增殖率、提高细胞存活率和抗凋亡能力的一种机制。
