Calcitriol restores antiestrogen responsiveness in estrogen receptor negative breast cancer cells: A potential new therapeutic approach

BMC Cancer

Research Article

María J Ibarra-Sánchez¹  José Esparza-López¹  Javier Camacho²  Heriberto Medina-Franco³  David Ordaz-Rosado⁴  Lorenza Díaz⁴  David Barrera⁴  Fernando Larrea⁴  Ali Halhali⁴  Rocío García-Becerra⁴  Euclides Avila⁴  Nancy Santos-Martínez⁵  Janice García-Quiroz⁵ 

[1] Biochemistry Unit, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga No. 15, 14000, TlalpanMéxico, D.F, Mexico;Department of Pharmacology, Centro de Investigación y de Estudios Avanzados, I.P.N., Av. Instituto Politécnico Nacional 2508 Gustavo A. Madero, 07360, México, D.F, Mexico;Department of Surgery, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga No. 15, 14000, TlalpanMéxico, D.F, Mexico;Departments of Reproductive Biology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga No. 15, 14000, TlalpanMéxico, Mexico;Departments of Reproductive Biology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga No. 15, 14000, TlalpanMéxico, Mexico;Department of Pharmacology, Centro de Investigación y de Estudios Avanzados, I.P.N., Av. Instituto Politécnico Nacional 2508 Gustavo A. Madero, 07360, México, D.F, Mexico;

关键词: Estrogen receptor;    Breast cancer;    Hormonal therapy;    Calcitriol;    VDR;   

DOI  :  10.1186/1471-2407-14-230

 received in 2013-09-24, accepted in 2014-03-25,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundApproximately 30% of breast tumors do not express the estrogen receptor (ER) α, which is necessary for endocrine therapy approaches. Studies are ongoing in order to restore ERα expression in ERα-negative breast cancer. The aim of the present study was to determine if calcitriol induces ERα expression in ER-negative breast cancer cells, thus restoring antiestrogen responses.MethodsCultured cells derived from ERα-negative breast tumors and an ERα-negative breast cancer cell line (SUM-229PE) were treated with calcitriol and ERα expression was assessed by real time PCR and western blots. The ERα functionality was evaluated by prolactin gene expression analysis. In addition, the effects of antiestrogens were assessed by growth assay using the XTT method. Gene expression of cyclin D1 (CCND1), and Ether-à-go-go 1 (EAG1) was also evaluated in cells treated with calcitriol alone or in combination with estradiol or ICI-182,780. Statistical analyses were determined by one-way ANOVA.ResultsCalcitriol was able to induce the expression of a functional ERα in ER-negative breast cancer cells. This effect was mediated through the vitamin D receptor (VDR), since it was abrogated by a VDR antagonist. Interestingly, the calcitriol-induced ERα restored the response to antiestrogens by inhibiting cell proliferation. In addition, calcitriol-treated cells in the presence of ICI-182,780 resulted in a significant reduction of two important cell proliferation regulators CCND1 and EAG1.ConclusionsCalcitriol induced the expression of ERα and restored the response to antiestrogens in ERα-negative breast cancer cells. The combined treatment with calcitriol and antiestrogens could represent a new therapeutic strategy in ERα-negative breast cancer patients.

【 授权许可】

Unknown   
© Santos-Martínez et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.