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lüll Calcium channel TRPV6 as a potential therapeutic target in estrogen receptor-negative breast cancer Peters AA; Simpson PT; Bassett JJ; Lee JM; Da Silva L; Reid LE; Song S; Parat MO; Lakhani SR; Kenny PA; Roberts-Thomson SJ; Monteith GRMol Cancer Ther 2012[Oct]; 11 (10): 2158-68Calcium 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.|Breast Neoplasms/genetics/*metabolism/pathology[MESH]|Calcium Channels/genetics/*metabolism[MESH]|Calcium/metabolism[MESH]|Cell Count[MESH]|Cell Cycle[MESH]|Cell Line, Tumor[MESH]|Cell Movement[MESH]|Cell Survival[MESH]|Down-Regulation/genetics[MESH]|Female[MESH]|Gene Amplification/genetics[MESH]|Gene Dosage/genetics[MESH]|Gene Expression Regulation, Neoplastic[MESH]|Gene Knockdown Techniques[MESH]|Humans[MESH]|Receptors, Estrogen/*metabolism[MESH]|Survival Analysis[MESH]|TRPV Cation Channels/*antagonists & inhibitors/genetics/*metabolism[MESH] |