The University of Queensland, School of Pharmacy, Brisbane, Queensland, Australia, 4072.
Mol Cancer Ther. 2012 Oct;11(10):2158-68. doi: 10.1158/1535-7163.MCT-11-0965. Epub 2012 Jul 17.
Calcium signaling is a critical regulator of cell proliferation. Elevated expression of calcium channels and pumps is a characteristic of some cancers, including breast cancer. We show that the plasma membrane calcium channel TRPV6, which is highly selective for Ca(2+), is overexpressed in some breast cancer cell lines. Silencing of TRPV6 expression in a breast cancer cell line with increased endogenous TRPV6 expression leads to a reduction in basal calcium influx and cellular proliferation associated with a reduction in DNA synthesis. TRPV6 gene amplification was identified as one mechanism of TRPV6 overexpression in a subset of breast cancer cell lines and breast tumor samples. Analysis of two independent microarray expression datasets from breast tumor samples showed that increased TRPV6 expression is a feature of estrogen receptor (ER)-negative breast tumors encompassing the basal-like molecular subtype, as well as HER2-positive tumors. Breast cancer patients with high TRPV6 levels had decreased survival compared with patients with low or intermediate TRPV6 expression. Our findings suggest that inhibitors of TRPV6 may offer a novel therapeutic strategy for the treatment of ER-negative breast cancers.
钙信号是细胞增殖的关键调节剂。一些癌症（包括乳腺癌）的特征是钙通道和泵的表达升高。我们表明，对 Ca(2+) 具有高度选择性的质膜钙通道 TRPV6 在一些乳腺癌细胞系中过表达。在表达内源性 TRPV6 增加的乳腺癌细胞系中沉默 TRPV6 的表达会导致基础钙内流减少和与 DNA 合成减少相关的细胞增殖减少。TRPV6 基因扩增被确定为一些乳腺癌细胞系和乳腺癌肿瘤样本中 TRPV6 过表达的一种机制。对来自乳腺癌肿瘤样本的两个独立微阵列表达数据集的分析表明，TRPV6 表达增加是雌激素受体 (ER)-阴性乳腺癌的特征，包括基底样分子亚型以及 HER2 阳性肿瘤。与 TRPV6 水平低或中等的患者相比，TRPV6 水平高的乳腺癌患者的生存率降低。我们的研究结果表明，TRPV6 的抑制剂可能为治疗 ER 阴性乳腺癌提供一种新的治疗策略。
