Calcium channel TRPV6 as a potential therapeutic target in estrogen receptor-negative breast cancer

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Calcium / metabolism
  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Cell Count
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Movement
  • Cell Survival
  • Down-Regulation / genetics
  • Female
  • Gene Amplification / genetics
  • Gene Dosage / genetics
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Receptors, Estrogen / metabolism*
  • Survival Analysis
  • TRPV Cation Channels / antagonists & inhibitors*
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / metabolism*


  • Calcium Channels
  • Receptors, Estrogen
  • TRPV Cation Channels
  • TRPV6 protein, human
  • Calcium