title: Modulation of vitamin D receptor and estrogen receptor by 1,25(OH)2-vitamin D3 in T-47D human breast cancer cells.
abstract: 1,25(OH)2-Vitamin D3 inhibits breast cancer cell proliferation through interaction with the vitamin D receptor (VDR). Regulation of VDR is under the influence of several factors which include the functional ligand for this receptor (1,25(OH)2-vitamin D3) as well as heterologous steroid hormones. We evaluated the nature of homologous regulation in T-47D human breast cancer cells with a radiolabelled ligand binding assay and a ribonuclease protection assay for VDR. Significant VDR up-regulation, as measured by hormone binding assays, occurred with pre-incubations with 10(-9)M through 10(-6)M 1,25(OH)2-vitamin D3 (P < 0.05). A 7-fold VDR up-regulation with 10(-8)M 1,25(OH)2-vitamin D3 occurred at 4 h treatment and was not associated with an increase in VDR mRNA expression on ribonuclease protection assay. This supports the hypothesis that up-regulation of VDR is probably the result of ligand-induced stabilization of pre-existing receptor. All-trans-retinoic acid, the progesterone analog R-5020, and prednisone were found to induce heterologous up-regulation of the VDR. We then determined with ligand binding assays whether 1,25(OH)2-vitamin D3 could influence receptor levels for another hormone in a manner analogous to the heterologous regulation of VDR. Regulation of estrogen receptor (ER) by 1,25(OH)2-vitamin D3 was studied in T-47D and MDA-MB-231 breast cancer cells. Incubation of T-47D cells, which are ER (+), with 10(-8)M 1,25(OH)2-vitamin D3 did not result in up-regulation of ER. Yet estrogen binding was significantly up-regulated in a cell line that is ER(-), MDA-MB-231. The increased estrogen binding was associated with a shift in binding affinity and ribonuclease protection assay showed absence of ER mRNA in these cells, suggesting an up-regulation of estrogen binding proteins and not of the ER itself.
authors.affiliation: Department of Surgery, Lombardi Cancer Research Center, Georgetown University Medical Center, Washington, DC, USA.
authors.forename: F
authors.initials: F
authors.lastname: Davoodi
authors.forename: R V
authors.initials: RV
authors.lastname: Brenner
authors.forename: S R
authors.initials: SR
authors.lastname: Evans
authors.forename: L M
authors.initials: LM
authors.lastname: Schumaker
authors.forename: M
authors.initials: M
authors.lastname: Shabahang
authors.forename: R J
authors.initials: RJ
authors.lastname: Nauta
authors.forename: R R
authors.initials: RR
authors.lastname: Buras
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D002117:Calcitriol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D011869:Radioligand Assay; D018167:Receptors, Calcitriol / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D013256:Steroids / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D018167:Receptors, Calcitriol; D011960:Receptors, Estrogen; D013256:Steroids; D002117:Calcitriol