This Article Full Text Full Text (PDF) Correction (v7,p1000) All Versions of this Article: 1535-7163.MCT-07-0478v1 7/2/271    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bolanz, K. A. Articles by Landowski, C. P. Search for Related Content PubMed PubMed Citation Articles by Bolanz, K. A. Articles by Landowski, C. P.

Research Articles: Therapeutics, Targets, and Development

The role of TRPV6 in breast carcinogenesis

Institute of Biochemistry and Molecular Medicine, University of Bern, Switzerland

Requests for reprints: Matthias A. Hediger, Institute of Biochemistry and Molecular Medicine, University of Bern, Bühlstrasse 28 CH-3012 Bern, Switzerland. E-mail: matthias.hediger{at}mci.unibe.ch

Abstract

TRPV6 is an endothelial calcium entry channel that is strongly expressed in breast adenocarcinoma tissue. In this study, we further confirmed this observation by analysis of breast cancer tissues, which indicated that TRPV6 mRNA expression was up-regulated between 2-fold and 15-fold compared with the average in normal breast tissue. Whereas TRPV6 is expressed in the cancer tissue, its role as a calcium channel in breast carcinogenesis is poorly understood. Therefore, we investigated how TRPV6 affects the viability, apoptosis, and calcium transport in the breast cancer cell line T47D. Hormones can also affect the tumor development; hence, we determined the effects of estradiol, progesterone, and 1,25-vitamin D on TRPV6 transcription. Interestingly, the estrogen receptor antagonist tamoxifen reduced expression of TRPV6 and is able to inhibit its calcium transport activity (IC₅₀, 7.5 µmol/L). The in vitro model showed that TRPV6 can be regulated by estrogen, progesterone, tamoxifen, and 1,25-vitamin D and has a large influence on breast cancer cell proliferation. Moreover, the effect of tamoxifen on cell viability was enhanced when TRPV6 expression was silenced with small interfering RNA. TRPV6 may be a novel target for the development of calcium channel inhibitors to treat breast adenocarcinoma expressing TRPV6. [Mol Cancer Ther 2008;7(2):271–9]

Grant support: Swiss National Science Foundation (M.A. Hediger) and Bern Cancer League (C.P. Landowski).

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 7/17/07; revised 11/29/07; accepted 12/28/07.

This article has been cited by other articles:

				Article on TRPV6 in Breast Cancer Mol. Cancer Ther., April 1, 2008; 7(4): 1000 - 1000. [Full Text] [PDF]