Stable expression of the nuclear vitamin D receptor in the human prostatic carcinoma cell line JCA-1: Evidence that the antiproliferative effects of 1 alpha,25-dihydroxyvitamin D-3 are mediated exclusively through the genomic signaling pathway
Stable expression of the nuclear vitamin D receptor in the human prostatic carcinoma cell line JCA-1: Evidence that the antiproliferative effects of 1 alpha,25-dihydroxyvitamin D-3 are mediated exclusively through the genomic signaling pathway
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DOI：
10.1210/en.137.5.1554
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发表时间：
1996-05-01
期刊：
影响因子：
4.8
通讯作者：
Miller, GJ
中科院分区：
文献类型：
--
作者：
Hedlund, TE;Moffatt, KA;Miller, GJ
已发现开环类固醇激素1 α-25-二羟维生素D-3 [1，25-OH）（2）D-3]可调节人前列腺癌细胞的生长和分化，尽管介导这些作用的精确机制尚未确定。1，25-（OH）（2）D-3能够通过涉及膜相关受体的非基因组信号通路和涉及核维生素D受体（VDR）的基因组通路发挥作用。本研究的主要目的是直接评估细胞核VDR在介导1，25-（OH）（2）D-3对人前列腺癌细胞的生长抑制作用中的作用。使用细胞系JCA-1是因为其无法表达可检测数量的VDR，并且在生长研究中未受到1，25-（OH）（2）D-3的可测量影响。这些细胞用野生型VDR互补DNA构建体稳定转染，产生以下结果：1）高亲和力核VDR的表达，2）1，25-（OH）（2）D-3对生长的剂量依赖性抑制，3）与对照组相比，1，25-（OH）（2）D-3对24-羟化酶的上调显著增加。这些数据表明，细胞核VDR表达足以介导1，25（OH）（2）D-3对前列腺癌细胞的抗增殖作用。此外，由于立体异构体1 β，25-二羟基维生素D-3未能阻断这些抗增殖作用，我们得出结论，非基因组作用机制不是1，25-（OH）（2）D-3生长抑制所必需的。
The secosteroid hormone 1 alpha-25-dihydroxyvitamin D-3 [1,25-OH)(2)D-3] has been found to regulate the growth and differentiation of human prostate cancer cells, although the precise mechanisms mediating these effects have not been defined. 1,25-(OH)(2)D-3 is capable of acting through both nongenomic signaling pathways involving a membrane-associated receptor and genomic pathways involving the nuclear vitamin D receptor (VDR). The primary purpose of this study was to directly evaluate the role of the nuclear VDR in mediating the growth inhibitory effects of 1,25-(OH)(2)D-3 on human prostate cancer cells. The cell line JCA-1 was used because it fails to express detectable numbers of VDRs and is not measurably affected by 1,25-(OH)(2)D-3 in growth studies. These cells were stably transfected with a wild-type VDR complementary DNA construct producing the following results: 1) the expression of high affinity nuclear VDRs, 2) the dose-dependent inhibition of growth by 1,25-(OH)(2)D-3, and 3) a significant increase in 24-hydroxylase up-regulation by 1,25-(OH)(2)D-3 compared to that in controls. These data indicate that nuclear VDR expression is sufficient to mediate the antiproliferative effects of 1,25(OH)(2)D-3 on prostate cancer cells. In addition, because the stereoisomer 1 beta,25-dihydroxyvitamin D-3 failed to block these antiproliferative effects, we conclude that nongenomic mechanisms of action are not requisite for growth inhibition by 1,25-(OH)(2)D-3.