Regulation of steroid receptor expression by 1alpha-hydroxyvitamin D5 in hormone-responsive breast cancer cells.
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.


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.


CONCLUSIONS
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.
Hussain-Hakimjee
Erum A
EA
Department of Surgical Oncology, University of Illinois at Chicago, Chicago, IL, USA.
Mehta
Rajendra G
RG
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D006801:Humans; D006887:Hydroxycholecalciferols / Q000494:pharmacology*; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
C103958:1-hydroxyvitamin D5; D006887:Hydroxycholecalciferols; D012333:RNA, Messenger; D018167:Receptors, Calcitriol