Systematic search for 1 alpha,25-dihydroxy-vitamin D3 receptors in human breast carcinomas

We looked systematically for the presence of receptor like binding sites for 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) in the cytosol from 22 breast cancers. Cytosols were centrifuged on 5-20% sucrose gradients after labeling with tritiated 1,25 (OH)2D3 (3H-1,25(OH)2D3 or 25-hydroxyvitamin D3 (25(OH)D3 alone or in the presence of a large excess of these unlabeled sterols. Binding sites for 1,25 (OH)2D3 migrating in the 3.5-3.7 S region were found in 7 out of 22 cancers, while 5.5-6.5 binding sites for 25 (OH)D3 were found in all cytosols. In a patient in whom cytosol containing a 3.5-3.7 S binding site was in sufficient amount, quantification of 1,25 (OH)2D3 binding indicated a KD of 0.28 nM and a maximal binding capacity of 0.15 pmol/mg prot. No relation was found between the presence or the absence of 1,25 (OH)2D3 binding sites and the histological type, the extension of the cancer, the presence of radiological or histological calcifications, the amount of estrogen or progesterone receptors, the plasma calcium or phosphate concentration and the emergence of metastases after 1 year. The significance of the presence of receptor-like binding sites for 1,25-(OH)2D3 in one third of breast cancers remains therefore unknown at the present time.