Calcium Channel TRPV6 as a Potential Therapeutic Target in Estrogen Receptor-Negative Breast Cancer

Amelia A. Peters, Peter T. Simpson, Johnathon J. Bassett, Jane M. Lee, Leonard Da Silva, Lynne E. Reid, Sarah Song, Marie Odile Parat, Sunil R. Lakhani, Paraic A. Kenny, Sarah J. Roberts-Thomson, Gregory R. Monteith

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

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 Ca2+, 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.

Original languageEnglish (US)
Pages (from-to)2158-2168
Number of pages11
JournalMolecular cancer therapeutics
Volume11
Issue number10
DOIs
StatePublished - Oct 1 2012

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Peters, A. A., Simpson, P. T., Bassett, J. J., Lee, J. M., Da Silva, L., Reid, L. E., Song, S., Parat, M. O., Lakhani, S. R., Kenny, P. A., Roberts-Thomson, S. J., & Monteith, G. R. (2012). Calcium Channel TRPV6 as a Potential Therapeutic Target in Estrogen Receptor-Negative Breast Cancer. Molecular cancer therapeutics, 11(10), 2158-2168. https://doi.org/10.1158/1535-7163.MCT-11-0965