1α,25-Dihydroxyvitamin D3 Specifically Induces Its Own Metabolism in a Human Cancer Cell Line
1α,25-Dihydroxyvitamin D3 Specifically Induces Its Own Metabolism in a Human Cancer Cell Line
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1α,25-二羟基维生素 D3 在人类癌细胞系中特异性诱导其自身代谢
DOI：
10.1210/endo-114-4-1225
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发表时间：
1984
期刊：
影响因子：
4.8
通讯作者：
F. Mclean
中科院分区：
文献类型：
--
作者：
J. Eisman;Elizabeth Sher;L. Suva;R. Frampton;F. Mclean
人乳腺癌和恶性黑色素瘤细胞具有1α，25-二羟基维生素D3（1，25-（OH）2D 3）的特异性高亲和力受体。这些细胞的复制受到1，25-（OH）2D 3的影响，具有双相剂量反应，即低浓度刺激和高浓度抑制。在23、24和26碳羟基化的几种1，25-（OH）2D 3代谢物对受体的亲和力降低，但仍能在高浓度下抑制细胞复制;这些代谢物都不能刺激细胞生长。在这种情况下，它是相当感兴趣的T47-D乳腺癌细胞培养积极代谢1，25-（OH）2D 3氯仿和水溶性化合物。基于多溶剂高压液相色谱、双标记研究和高碘酸盐灵敏度，很明显代谢发生在23、24和26、27碳原子附近。三种代谢产物已被初步鉴定为1，24，25-（OH）3D 3和1，25-（OH）2D的24-氧代衍生物。
Human breast cancer and malignant melanoma cells possess specific, high affinity receptors for 1α,25-dihy-droxyvitamin D3 (1,25-(OH)2D3.) The replication of these cells is affected by 1,25-(OH)2D3 with a biphasic dose response, i.e. stimulation at low concentration and inhibition at high concentration. Several 1,25-(OH)2D3 metabolites hydroxylated at the 23, 24 and 26 carbons have reduced affinity for the receptors but are still able to inhibit cell replication at high concentrations; none of these metabolites are able to stimulate cell growth. In this context, it is of considerable interest that T47-D breast cancer cells in culture actively metabolize 1,25-(OH)2D3 to chloroform- and aqueous-soluble compounds. Based on multiple solvent high pressure liquid chromatography, double label studies, and periodate sensitivity it is apparent that metabolism occurs about the 23,24 and 26,27 carbon atoms. Three metabolites have been tentatively identified as 1,24,25-(OH)3D3 and the 24-oxo derivatives of 1,25-(OH)2D...