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Targeting 1α,25-dihydroxyvitamin D3antiproliferative insensitivity in breast cancer cells by co-treatment with histone deacetylation inhibitors

The Journal of Steroid Biochemistry and Molecular Biology
Publication Date
DOI: 10.1016/j.jsbmb.2004.03.081
  • Histone Deacetylation
  • Ncor1
  • Chemotherapy
  • Biology
  • Medicine


Abstract Proliferation of the non-malignant breast epithelial cell line, MCF-12A, is sensitively and completely inhibited by 1α,25-dihydroxyvitamin D 3 (1α,25(OH) 2D 3) (ED 90=70 nM), We used real time RT-PCR to demonstrate that the relative resistance to 1α,25(OH) 2D 3 of MDA-MB-231 cells (ED 50>100 nM) correlated with significantly reduced Vitamin D receptor (VDR) and increased NCoR1 nuclear receptor co-repressor mRNA (0.1-fold reduction in VDR and 1.7-fold increase in NCoR1 relative to MCF-12A ( P<0.05)). This molecular lesion can be targeted by co-treating cells with 1α,25(OH) 2D 3 or potent analogs and the histone deacetylation inhibitor trichostatin A (TSA). For example, the co-treatment of 1,25-dihydroxy-16,23,Z-diene-26,27-hexafluoro-19-nor Vitamin D 3 (RO-26-2198) (100 nM) plus TSA results in strong additive antiproliferative effects in MDA-MB-231 cells. This may represent novel chemotherapeutic regime for hormone insensitive breast cancer.

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