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1α,25‐dihydroxyvitamin D regulates vascular endothelial growth factor and hypoxia‐inducible factor‐1α in breast epithelial cells
Author(s) -
Jiang Yan,
Teegarden Dorothy
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.887.4
Subject(s) - vascular endothelial growth factor , transfection , hypoxia inducible factors , hypoxia (environmental) , chemistry , messenger rna , cancer research , biology , endocrinology , microbiology and biotechnology , vegf receptors , cell culture , gene , biochemistry , organic chemistry , oxygen , genetics
The angiogenic vascular endothelial growth factor (VEGF) has been shown to be differentially regulated by 1α, 25‐dihydroxyvitamin D (1,25(OH) 2 D) in untransformed cells and cancer cells, but the effect at different stages of cancer progression has not been investigated in breast epithelial cells. Evidence also suggests that 1,25(OH) 2 D reduces VEGF expression through stabilization of hypoxia‐inducible factor (HIF)‐1α, a direct transcriptional regulator of VEGF. The purpose of this study was to determine the impact of 1,25(OH) 2 D on VEGF expression in untransformed and H‐ ras transfected MCF10A breast epithelial cells. Compared to vehicle, 1,25(OH) 2 D treatment (24 hrs) significantly reduced VEGF mRNA expression in a dose‐dependent manner, with significance achieved at 1 nM (25%) in untransformed cells. Similarly, with 1,25(OH) 2 D (1 nM) treatment, mRNA expression of HIF‐1α was also significantly decreased by 32% compared to vehicle in untransformed cells. In ras ‐transfected MCF10A cells, 1,25(OH) 2 D‐mediated reduction of VEGF (28%) and HIF‐1α (34%) mRNA was achieved only at a higher dose (10 nM and 100nM, respectively) compared to vehicle. These results suggest that in breast cells, 1,25(OH) 2 D‐induced suppression of VEGF may occur through the transcriptional regulation of HIF‐1α, and the effect may be reduced in the presence of the H‐ ras oncogene. Supported by NIH DK069965.