VITAMIN-D RECEPTORS IN BREAST-CANCER CELLS

1,25-(OH)(2)-Vitamin D-3, the active metabolite of vitamin D, is a sec osteroid 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 D-3 has been documented in osteosarcoma, melan oma, colon carcinoma, and breast carcinoma cells. This study was desig ned to analyze vitamin D receptor level in breast cancer cells as a ma rker of differentiation and as a predictor of growth inhibition by 1,2 5-(OH)(2)-vitamin D-3. VDR messenger RNA was found to be present in re latively 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 g rowth inhibition by 10(-9) M 1,25-(OH)(2)-vitamin D-3 (p < 0.05). MDA- MB-231 cells, which have very low levels of VDR, demonstrated no growt h inhibition by 1,25-(OH)(2)-vitamin D-3 at concentrations up to 10(-6 ) M. Based on these results it can be stated that VDR expression is lo st with de-differentiation and that receptor is essential for the anti proliferative response to 1,25-(OH)(2)-vitamin D-3.