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Regulation of steroid receptor expression by 1alpha-hydroxyvitamin D5 in hormone-responsive breast cancer cells
Erum A Hussain-Hakimjee1, Rajendra G Mehta
1Department of Surgical Oncology, University of Illinois at Chicago, Chicago, IL, USA.
Background:
Vitamin D analog, 1alpha-hydroxy-24-ethyl-cholecalciferol (1alpha(OH)D5), is a less toxic VDR agonist that suppresses proliferation of breast cancer cells in vitro and in vivo. The present study assessed 1alpha(OH)D5-mediated regulation of VDR, and its potential anti-estrogenic activity in BT-474 cells.
Materials And Methods:
The mRNA and protein expression of steroid receptors were determined using RT-PCR and Western blot analyses, respectively.
Results:
VDR mRNA was up-regulated (180% of control) by 1alpha(OH)D5 within seven hours, whereas the expression of VDR protein increased by two-fold in 24 hours. This increase was abolished in presence of either actinomycin D or cyclohexamide. Additionally, there was a four-fold decrease in ERalpha mRNA and 40% decrease in ERalpha protein after 28 and 48 hours following 1alpha(OH)D5 treatment, respectively. Down-regulation of some of the estrogen-inducible genes was observed.
Conclusion:
Although no VDR stabilization by 1alpha(OH)D5 was observed, there was an increased expression of the VDR followed by partial anti-estrogenic activity in hormone-responsive BT-474 cells.
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