1α, 25-Dihydroxyvitamin D regulates hypoxia-inducible factor-1α in untransformed and Harvey-ras transfected breast epithelial cells

The purpose of this study was to determine the mechanism by which la 25-dihydroxyvitamin D (1 25(OH)(2)D) alters hypoxia-inducible factor-1 alpha (HIF-1 alpha) protein in untransformed and Harvey-ras (H-ras) oncogene transfected MCF10A breast epithelial cells Treatment with 1 25(OH)(2)D (10 nM) Increased both mRNA (2 55 +/- 6-fold vs vehicle p = 0 03) and protein levels (2 37 +/- 3-fold vs vehicle p < 0 0001) of HIF-1 alpha in MCF10A cells in 12 h which remained elevated at 24 h However in H-ras transfected MCF10A cells 1 25(OH)(2)D treatment Increased HIF-1a protein level (2 08 +/- 38-fold vs vehicle p = 0 05) at 12 h with no change in mRNA level and HIF-1a protein level returned to baseline after 24 h A transcription inhibitor prevented the 1 25(OH)2D induction of HIF-1a protein and mRNA levels in MCF10A cells but failed to alter the induction of HIF-1 alpha protein level in H-ras transfected MCF10A cells On the other hand inhibition of proteasomal degradation prevented the 1 25(OH)(2)D-induced HIF-1 alpha protein level in H-ras transfected MCF10A but not in MCF10A cells These results support that 1 25(OH)2D regulates HIF-1 alpha protein level via transcriptional regulation in MCF10A cells in contrast to through proteosomal degradation with the presence of H-ras oncogene in MCF10A cells (C) 2010 Elsevier Ireland Ltd All rights reserved