Bolanz Katrin A, Hediger Matthias A, Landowski Christopher P
Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland.
Mol Cancer Ther. 2008 Feb;7(2):271-9. doi: 10.1158/1535-7163.MCT-07-0478. Epub 2008 Feb 1.
TRPV6 is an endothelial calcium entry channel that is strongly expressed in breast adenocarcinoma tissue. In this study, we further confirmed this observation by analysis of breast cancer tissues, which indicated that TRPV6 mRNA expression was up-regulated between 2-fold and 15-fold compared with the average in normal breast tissue. Whereas TRPV6 is expressed in the cancer tissue, its role as a calcium channel in breast carcinogenesis is poorly understood. Therefore, we investigated how TRPV6 affects the viability, apoptosis, and calcium transport in the breast cancer cell line T47D. Hormones can also affect the tumor development; hence, we determined the effects of estradiol, progesterone, and 1,25-vitamin D on TRPV6 transcription. Interestingly, the estrogen receptor antagonist tamoxifen reduced expression of TRPV6 and is able to inhibit its calcium transport activity (IC(50), 7.5 micromol/L). The in vitro model showed that TRPV6 can be regulated by estrogen, progesterone, tamoxifen, and 1,25-vitamin D and has a large influence on breast cancer cell proliferation. Moreover, the effect of tamoxifen on cell viability was enhanced when TRPV6 expression was silenced with small interfering RNA. TRPV6 may be a novel target for the development of calcium channel inhibitors to treat breast adenocarcinoma expressing TRPV6.
瞬时受体电位香草酸亚型6（TRPV6）是一种内皮钙内流通道，在乳腺腺癌组织中强烈表达。在本研究中，我们通过对乳腺癌组织的分析进一步证实了这一观察结果，结果表明TRPV6信使核糖核酸（mRNA）表达与正常乳腺组织的平均水平相比上调了2至15倍。虽然TRPV6在癌组织中表达，但其作为钙通道在乳腺癌发生中的作用却知之甚少。因此，我们研究了TRPV6如何影响乳腺癌细胞系T47D的活力、凋亡和钙转运。激素也会影响肿瘤的发展；因此，我们确定了雌二醇、孕酮和1,25-维生素D对TRPV6转录的影响。有趣的是，雌激素受体拮抗剂他莫昔芬降低了TRPV6的表达，并能够抑制其钙转运活性（半数抑制浓度（IC(50)），7.5微摩尔/升）。体外模型表明，TRPV6可受雌激素、孕酮、他莫昔芬和1,25-维生素D的调节，并对乳腺癌细胞增殖有很大影响。此外，当用小干扰RNA沉默TRPV6表达时，他莫昔芬对细胞活力的影响增强。TRPV6可能是开发钙通道抑制剂以治疗表达TRPV6的乳腺腺癌的一个新靶点。
