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

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BMC Cancer

, 14:230

Cell and molecular biology


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.

KeywordsEstrogen receptor Breast cancer Hormonal therapy Calcitriol VDR AbbreviationsCTSDCathepsin D

CCND1Cyclin D1


EAG1Ether-à-go-go 1

EC50Stimulatory concentration

EGFRHuman epidermal growth factor receptor- 1

EREstrogen receptor

FBSFetal bovine serum

GAPDHGlyceraldehyde-3-phosphate dehydrogenase

HER2Human epidermal growth factor receptor- 2

MAPKMitogen-activated protein kinase

PRProgesterone receptor


qPCRReal time polymerase chain reaction

RTReverse transcription

S.DStandard deviation

TFF1Trefoil factor 1

VDRVitamin D receptor.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-14-230 contains supplementary material, which is available to authorized users.

Nancy Santos-Martínez, Lorenza Díaz contributed equally to this work.

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Autor: Nancy Santos-Martínez - Lorenza Díaz - David Ordaz-Rosado - Janice García-Quiroz - David Barrera - Euclides Avila - Ali 


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