Skowronski R J, Peehl D M, Feldman D
Department of Medicine, Stanford University School of Medicine, California 94305.
Endocrinology. 1993 May;132(5):1952-60. doi: 10.1210/endo.132.5.7682937.
It has been suggested that vitamin D deficiency may promote prostate cancer, although the mechanism is not understood. In this study three human prostate carcinoma cell lines, LNCaP, DU-145, and PC-3, were examined both for the presence of specific 1,25 dihydroxyvitamin D3 [1,25(OH)2D3] receptors (VDRs) and also employed to study the effects of hormone on cell proliferation and differentiation. Ligand binding experiments demonstrated classical VDR in all three cell lines examined with an apparent dissociation constant of 7.5, 5.4, and 6.3 x 10(-11) M for LNCaP, DU-145, and PC-3 cells, respectively. Corresponding binding capacity for the three prostate carcinoma cell lines were 27, 31, and 78 fmol/mg protein, respectively. The presence of VDR in the three cell lines was also confirmed by immunocytochemistry. In addition, one major 4.6-kilobase messenger RNA transcript hybridizing with a specific human VDR complementary DNA probe was identified in all three cell lines. Interestingly, both DU-145 and PC-3 but not LNCaP cell lines exhibited 1,25(OH)2D3-stimulated induction of 24-hydroxylase messenger RNA employed as a marker of 1,25(OH)2D3 action. Physiological levels of 1,25(OH)2D3 dramatically inhibited proliferation of the LNCaP and PC-3 cell lines. However, in spite of the presence of high affinity VDR, proliferation of DU-145 cells was not inhibited by 1,25(OH)2D3 at the doses tested. Treatment with 1,25(OH)2D3 caused a dose-dependent stimulation of prostate-specific antigen secretion by LNCaP cells. In conclusion, these results demonstrate that these three human prostate carcinoma cell lines all possess specific VDR and that 1,25(OH)2D3 treatment can elicit both an antiproliferative and a differentiating action on these cancer cells. The findings lend support to the hypothesis that vitamin D might exert beneficial actions on prostate cancer risk.
有人提出维生素D缺乏可能会促进前列腺癌的发生，尽管其机制尚不清楚。在本研究中，对三种人前列腺癌细胞系LNCaP、DU - 145和PC - 3进行了检查，以确定是否存在特异性的1,25 - 二羟维生素D3 [1,25(OH)2D3]受体（VDR），并用于研究激素对细胞增殖和分化的影响。配体结合实验表明，在所检测的所有三种细胞系中均存在经典的VDR，LNCaP、DU - 145和PC - 3细胞的表观解离常数分别为7.5、5.4和6.3×10(-11) M。三种前列腺癌细胞系的相应结合能力分别为27、31和78 fmol/mg蛋白。免疫细胞化学也证实了三种细胞系中存在VDR。此外，在所有三种细胞系中均鉴定出一种与特异性人VDR互补DNA探针杂交的主要4.6千碱基信使RNA转录本。有趣的是，DU - 145和PC - 3细胞系而非LNCaP细胞系表现出1,25(OH)2D3刺激诱导的24 - 羟化酶信使RNA，该信使RNA用作1,25(OH)2D3作用的标志物。生理水平的1,25(OH)2D3显著抑制LNCaP和PC - 3细胞系的增殖。然而，尽管存在高亲和力的VDR，但在所测试的剂量下，DU - 145细胞的增殖并未受到1,25(OH)2D3的抑制。用1,25(OH)2D3处理导致LNCaP细胞分泌前列腺特异性抗原呈剂量依赖性刺激。总之，这些结果表明这三种人前列腺癌细胞系均具有特异性VDR，并且1,25(OH)2D3处理可对这些癌细胞产生抗增殖和分化作用。这些发现支持了维生素D可能对前列腺癌风险发挥有益作用的假说。
