title: 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.
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 (Ca(2+)) pumps, Ca(2+) channels and Ca(2+)-binding proteins. Also, it is known that deregulated Ca(2+) homeostasis has been implicated in the pathophysiology of breast. The L-type Ca(2+) 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 Ca(2+)-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 Ca(2+)-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 Ca(2+) signaling.
authors.affiliation: Faculdade de Ciências da Saúde, CICS-UBI - Health Sciences Research Center, University of Beira Interior, Av. Infante D. Henrique, 6200-506, Covilhã, Portugal.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Marques
authors.forename: Carina G
authors.initials: CG
authors.lastname: Peres
authors.forename: Cátia V
authors.initials: CV
authors.lastname: Vaz
authors.forename: Inês M
authors.initials: IM
authors.lastname: Gomes
authors.forename: Marília I
authors.initials: MI
authors.lastname: Figueira
authors.forename: Elisa
authors.initials: E
authors.lastname: Cairrão
authors.forename: Ignacio
authors.initials: I
authors.lastname: Verde
authors.forename: Cláudio J
authors.initials: CJ
authors.lastname: Maia
authors.forename: Sílvia
authors.initials: S
authors.lastname: Socorro
mesh_terms: D020746:Calcium Channels, L-Type / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D013196:Dihydrotestosterone / Q000378:metabolism* / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
chemical_list: D020746:Calcium Channels, L-Type; D002135:Calcium-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C513323:RGN protein, human; D013196:Dihydrotestosterone