VITAMIN-D RECEPTORS IN BREAST-CANCER CELLS
VITAMIN-D RECEPTORS IN BREAST-CANCER CELLS
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DOI：
10.1007/bf00666153
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发表时间：
1994-01-01
影响因子：
3.8
通讯作者：
EVANS, SRT
中科院分区：
文献类型：
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作者：
BURAS, RR;SCHUMAKER, LM;EVANS, SRT
1，25-（OH）（2）-维生素D-3是维生素D的活性代谢物，是一种已知在白血病细胞中具有分化活性的开环甾类激素。研究表明，维生素D受体（VDR）存在于广泛的组织和细胞类型中。1，25-（OH）（2）-维生素D-3的抗增殖活性已在骨肉瘤、黑色素瘤、结肠癌和乳腺癌细胞中得到证实。本研究旨在分析乳腺癌细胞中维生素D受体水平作为分化的标志和作为1，25-（OH）（2）-维生素D-3生长抑制的预测因子。发现VDR信使RNA在高分化细胞中以相对高的水平存在，而在低分化细胞中以低的水平存在。所有细胞系均具有可检测的VDR mRNA。放射性标记配体结合试验显示相似的模式。以中等水平表达VDR的MCF-7和T47 D细胞显示出10（-9）M 1，25-（OH）（2）-维生素D-3的显著生长抑制（p < 0.05）。VDR水平极低的MDA-MB-231细胞在浓度高达10（-6）M时未显示出1，25-（OH）（2）-维生素D-3的生长抑制作用。基于这些结果，可以说VDR表达随着去分化而丧失，并且受体对于对1，25-（OH）（2）-维生素D-3的抗增殖应答是必需的。
1,25-(OH)(2)-Vitamin D-3, 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 D-3 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 D-3.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) M 1,25-(OH)(2)-vitamin D-3 (p < 0.05). MDA-MB-231 cells, which have very low levels of VDR, demonstrated no growth 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 lost with de-differentiation and that receptor is essential for the antiproliferative response to 1,25-(OH)(2)-vitamin D-3.