Regulation of estrogen receptor-α gene expression by 1,25- dihydroxyvitamin D in MCF-7 cells

Adriana Stoica, Miguel Saceda, Amina Fakhro, Harrison B. Solomon, Bradley D. Fenster, Mary Beth Martin

    Research output: Contribution to journalArticle

    65 Citations (Scopus)

    Abstract

    This report describes an investigation of the role of 1,25- dihydroxyvitamin D (VD3) in the regulation of estrogen receptor-α (ER) in the ER-positive breast cancer cell line, MCF-7. Treatment of cells with 10 nM VD3 resulted in a 50% decline in the concentration of ER protein at 24 h. Scatchard analysis showed a corresponding decrease in the number of estradiol binding sites and no alteration in the binding affinity of estradiol for the ER (K(d) = 0.08 nM in VD3-treated cells compared with K(d) = 0.07 nM in control cells). Vitamin D treatment also caused a 50% decrease in the steady state amount of ER mRNA, which was maximal by 18 h. In vitro transcription run-on experiments demonstrated a decrease of approximately 60% in transcription of the estrogen receptor gene. Transient transfections using an ER promoter-CAT construct also demonstrated a 40% decrease in CAT activity after VD3 treatment. Sequence analysis identified a potential vitamin D response element (nVDRE) within the ER promoter. When this element was mutated, the ability of VD3 to block transcription from the ER promoter was lost. When the nVDRE was placed upstream of a heterologous promoter, nVDRE- SV40-CAT, treatment with VD3 resulted in a 50% decrease in CAT activity. Interestingly, co-transfection of either the ER promoter-CAT or the nVDRE- SV40-CAT construct and a vitamin D receptor expression vector into COS-1 or CV-1 cells showed an approximately 4-fold increase in CAT activity after VD3 treatment. Taken together these data suggest that VD3 inhibition of ER gene transcription is mediated through a nVDRE in the ER promoter. Inhibition appears to be cell specific.

    Original languageEnglish
    Pages (from-to)640-651
    Number of pages12
    JournalJournal of Cellular Biochemistry
    Volume75
    Issue number4
    DOIs
    Publication statusPublished - 15 Dec 1999

    Keywords

    • 1,25-dihydroxyvitamin 3
    • ER
    • MCF-7 cells

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

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