Sex steroids induced up-regulation of 1,25-(OH)2 vitamin D3 receptors in T 47D breast cancer cells.
There is evidence indicating that 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] through binding to its specific receptor (VDR) exerts an antiproliferative effect on breast cancer cells. Considering the importance of receptor regulation in modulating the target cell responsiveness to hormones, the effect of dihydrotestosterone (DHT) and estradiol-17 beta (E2) on the regulation of VDR number was investigated in T 47D human breast cancer cells that also express androgen and estrogen (ER) receptors. T 47D cells were grown in RPMI medium containing 10% charcoal-treated fetal calf serum and the receptor content was determined in cells at confluence. Whole cell binding studies confirmed the presence of highly specific, saturable (4.01 +/- 1.82 fmol/10(6) cells), high affinity (Kd = 0.079 +/- 0.058 x 10(-9) M) 1,25(OH)2D3 receptors in control cells. Exposure to 10(-7) M DHT for 72 h resulted in a significant increase in VDR levels. Similar results were obtained with 10(-7) M E2. DHT- and E2-induced up-regulation was completely suppressed by 10(-6) M tamoxifen (TAM) addition but unaffected by 10(-6) M flutamide. TAM treatment alone produced a significant dose-dependent increase in VDR content, that was maximal at 10(-6) M. Our data strongly suggest, for the first time, an up-regulation of VDR by DHT and E2 via an ER-mediated mechanism.
Escaleira
M T
MT
Departamento de Clínica Médica, Faculdade de Medicina, Universidade de São Paulo, Brazil.
Sonohara
S
S
Brentani
M M
MM
D001943:Breast Neoplasms / Q000378:metabolism*; D002117:Calcitriol / Q000378:metabolism; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D005485:Flutamide / Q000494:pharmacology; D006801:Humans; D011944:Receptors, Androgen / Q000378:metabolism; D018167:Receptors, Calcitriol; D011960:Receptors, Estrogen / Q000378:metabolism; D011987:Receptors, Steroid / Q000187:drug effects* / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects*
D011944:Receptors, Androgen; D018167:Receptors, Calcitriol; D011960:Receptors, Estrogen; D011987:Receptors, Steroid; D013196:Dihydrotestosterone; D013629:Tamoxifen; D004958:Estradiol; D005485:Flutamide; D002117:Calcitriol