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5α-Dihydrotestosterone regulates the expression of L-type calcium channels and calcium-binding protein regucalcin in human breast cancer cells with suppression of cell growth

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Abstract

Androgens have been associated with the development of normal breast, and their role in mammary gland carcinogenesis has also been described. Several studies reported that androgens inhibit breast cancer cell growth, whereas others linked their action with the modulation of calcium (Ca2+) pumps, Ca2+ channels and Ca2+-binding proteins. Also, it is known that deregulated Ca2+ homeostasis has been implicated in the pathophysiology of breast. The L-type Ca2+ channels (LTCCs) were found to be up-regulated in colon, colorectal and prostate cancer, but their presence in breast tissues remains uncharacterized. On the other hand, regucalcin (RGN) is a Ca2+-binding protein involved in the control of mammary gland cell proliferation, which has been identified as an androgen target gene in distinct tissues except breast. This study aimed to confirm the expression and activity of LTCCs in human breast cancer cells and investigate the effect of androgens in regulating the expression of α1C subunit (Cav1.2) of LTCCs and Ca2+-binding protein RGN. PCR, Western blot, immunofluorescence and electrophysiological experiments demonstrated the expression and activity of Cav1.2 subunit in MCF-7 cells. The MCF-7 cells were treated with 1, 10 or 100 nM of 5α-dihydrotestosterone (DHT) for 24–72 h. The obtained results showed that 1 nM DHT up-regulated the expression of Cav1.2 subunit while diminishing RGN protein levels, which was underpinned by reduced cell viability. These findings first confirmed the presence of LTCCs in breast cancer cells and opened new perspectives for the development of therapeutic approaches targeting Ca2+ signaling.

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Acknowledgments

This work was partially supported by the Portuguese Foundation for Science and Technology (FCT) under Program COMPETE (PEst-OE/SAU/UI0709/2014). Cátia V. Vaz and Ricardo Marques were funded by FCT fellowships (SFRH/BD/70316/2010 and SFRH/BD/66875/2009, respectively).

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  1. Faculdade de Ciências da Saúde, CICS-UBI - Health Sciences Research Center, University of Beira Interior, Av. Infante D. Henrique, 6200-506, Covilhã, Portugal

    Ricardo Marques, Carina G. Peres, Cátia V. Vaz, Inês M. Gomes, Marília I. Figueira, Elisa Cairrão, Ignacio Verde, Cláudio J. Maia & Sílvia Socorro

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  1. Ricardo Marques
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  2. Carina G. Peres
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Marques, R., Peres, C.G., Vaz, C.V. et al. 5α-Dihydrotestosterone regulates the expression of L-type calcium channels and calcium-binding protein regucalcin in human breast cancer cells with suppression of cell growth. Med Oncol 32, 228 (2015). https://doi.org/10.1007/s12032-015-0676-x

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