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Tamoxifen inhibits TRPV6 activity via estrogen receptor independent pathways in TRPV6 transfected MCF‐7 cells
Author(s) -
Bolanz Katrin Annika,
Kovacs Gergely Gyula,
Landowski Christopher Paul,
Hediger Matthias A
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.998.29
Subject(s) - trpv6 , tamoxifen , estrogen receptor , transfection , calcium , endocrinology , chemistry , medicine , selective estrogen receptor modulator , antiestrogen , estrogen , cancer research , calcium metabolism , biology , breast cancer , cancer , biochemistry , gene
TRPV6 expression has been shown to be upregulated in breast cancer tissue compared to normal mammary gland tissue. In several cell lines, it was shown that knockdown of TRPV6 inhibits cell growth. Tamoxifen is a selective estrogen receptor modulator widely used in breast cancer therapy. Previously, we showed that tamoxifen down regulates TRPV6 mRNA expression and that it also inhibits calcium uptake in TRPV6‐transfected oocytes. In the present study we examined the effect of tamoxifen on TRPV6 function in MCF‐7 breast cancer cells transiently transfected with TRPV6, tagged with EYFP. TRPV6 function was measured with fluorescence microscopy using Fura‐2. The influx of calcium, barium and manganese was significantly larger in cells transfected with this construct, compared to non‐transfected cells. In transfected cells, 10 µM tamoxifen induced a decrease in intracellular calcium concentration in transfected cells down to the basal calcium level of non‐transfected cells, following a large, transient increase. In nominally calcium free buffer tamoxifen induced a smaller transient increase. The transport rate of calcium and barium but not manganese was decreased 50‐70% by tamoxifen. This inhibitory effect was not mediated by estrogen receptors as the antiestrogen ICI 182,720 had no inhibitory effect. Inhibition of PI3K with 25 µM LY294002 had no effect on TRPV6 activity. These findings give novel insights into how tamoxifen might be effective in estrogen receptor negative breast cancer patients. Our data suggest that TRPV6 is involved in the therapeutic mechanism of tamoxifen during breast cancer treatment. This study was supported by the Novartis Stiftung and the Bernische Krebsliga (PI's Hediger and Landowski).