Vitamin D receptors in breast cancer cells.
1,25-(OH)2-Vitamin D3, the active metabolite of vitamin D, is a secosteroid hormone with known differentiating activity in leukemic cells. Studies have demonstrated the presence of vitamin D receptors (VDR) in a wide range of tissues and cell types. Antiproliferative activity of 1,25-(OH)2-vitamin D3 has been documented in osteosarcoma, melanoma, colon carcinoma, and breast carcinoma cells. This study was designed to analyze vitamin D receptor level in breast cancer cells as a marker of differentiation and as a predictor of growth inhibition by 1,25-(OH)2-vitamin D3. VDR messenger RNA was found to be present in relatively high levels in well-differentiated cells and in low levels in poorly differentiated cells. All cell lines had detectable VDR mRNA. Radiolabeled ligand binding assay showed a similar pattern. MCF-7 and T47D cells, which express VDR at moderate levels, showed significant growth inhibition by 10(-9) M1,25-(OH)2-vitamin D3 (p < 0.05). MDA-MB-231 cells, which have very low levels of VDR, demonstrated no growth inhibition by 1,25-(OH)2-vitamin D3 at concentrations up to 10(-6) M. Based on these results it can be stated that VDR expression is lost with de-differentiation and that receptor is essential for the antiproliferative response to 1,25-(OH)2-vitamin D3.
Buras
R R
RR
Department of Surgery, Georgetown University, Washington DC.
Schumaker
L M
LM
Davoodi
F
F
Brenner
R V
RV
Shabahang
M
M
Nauta
R J
RJ
Evans
S R
SR
D000230:Adenocarcinoma / Q000737:chemistry / Q000473:pathology; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000737:chemistry / Q000473:pathology*; D002117:Calcitriol / Q000494:pharmacology*; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry / Q000473:pathology; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D018076:DNA, Complementary / Q000235:genetics; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D009363:Neoplasm Proteins / Q000032:analysis / Q000502:physiology*; D010996:Pleural Effusion / Q000473:pathology; D018167:Receptors, Calcitriol / Q000032:analysis / Q000187:drug effects* / Q000502:physiology; D014407:Tumor Cells, Cultured
D016588:Anticarcinogenic Agents; D014408:Biomarkers, Tumor; D018076:DNA, Complementary; D006131:Growth Inhibitors; D009363:Neoplasm Proteins; D018167:Receptors, Calcitriol; D002117:Calcitriol