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

Peters, Amelia A., Simpson, Peter T., Bassett, Johnathon J., Lee, Jane M., Da Silva, Leonard, Reid, Lynne E., Song, Sarah, Parat, Marie-Odile, Lakhani, Sunil R., Kenny, Paraic A., Roberts-Thomson, Sarah J. and Monteith, Gregory R. (2012) Calcium channel TRPV6 as a potential therapeutic target in estrogen receptor negative breast cancer. Molecular Cancer Therapeutics, 11 10: 2158-2168.


Author Peters, Amelia A.
Simpson, Peter T.
Bassett, Johnathon J.
Lee, Jane M.
Da Silva, Leonard
Reid, Lynne E.
Song, Sarah
Parat, Marie-Odile
Lakhani, Sunil R.
Kenny, Paraic A.
Roberts-Thomson, Sarah J.
Monteith, Gregory R.
Title Calcium channel TRPV6 as a potential therapeutic target in estrogen receptor negative breast cancer
Journal name Molecular Cancer Therapeutics  (ERA 2012 Listed)    (ERA 2010 Rank A)   Check publisher's open access policy
Publication date 2012-07-17
Sub-type Article
DOI 10.1158/1535-7163.MCT-11-0965
Volume number 11
Issue number 10
ISSN 1535-7163;1538-8514
Start page 2158
End page 2168
Total pages 11
Place of publication Philadelphia, PA, United States
Publisher American Association for Cancer Research
Collection year 2013
Language eng
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 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 lead 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 sub-set 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 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 to patients with low or intermediate TRPV6 expression. Our findings suggest that inhibitors of TRPV6 may offer a novel therapeutic strategy for the treatment of estrogen receptor-negative breast cancers.
Keyword TRPV6
Breast cancer
Basal calcium
Copy number
Cell cycle
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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Created: Fri, 20 Jul 2012, 17:37:40 EST by Dr Sarah Song on behalf of Institute for Molecular Bioscience