Prostatic 25-hydroxyvitamin D-1α-hydroxylase and its implication in prostate cancer
Prostatic 25-hydroxyvitamin D-1α-hydroxylase and its implication in prostate cancer
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DOI：
10.1002/jcb.10342
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发表时间：
2003-02-01
影响因子：
4
通讯作者：
Holick, MF
中科院分区：
文献类型：
--
作者：
Chen, TC;Wang, LL;Holick, MF
有证据表明维生素 D 可能对前列腺癌具有保护作用。 1α,25-二羟基维生素 D [1α,25(OH)(2)D] 抑制前列腺细胞生长并诱导分化。 25-羟基维生素 D-1α-羟化酶 [1α-OHase] 是一种负责合成 1α,25(OH)(2)D 的酶，在培养的前列腺细胞中表达。我们观察到前列腺癌细胞中 1α-OHase 活性显着降低，表明这些细胞中 1α-OHase 存在某些缺陷。为了研究缺陷是否是由于启动子水平上的酶失调所致，合成了一系列启动子缺失构建体并将其整合到荧光素酶报告基因的上游。在转染的正常前列腺细胞系 (PZHPV-7) 中，鉴定出两个具有高基础活性的区域：1alpha-OHase 基因 ATG 起始位点上游的 -1100 bp (AN2) 和 -394 bp (AN5)。当带有 AN2 或 AN5 的报告基因转染到前列腺癌细胞系中时，我们观察到这两种构建体在 PC-3 细胞和 DU145 细胞中的基础启动子活性低于 PZHPV-7 细胞中的基础启动子活性，并且在 LNCaP 细胞中启动子活性丧失。因此，结果表明酶活性的缺陷可能是由于前列腺癌细胞中启动子活性降低造成的。 J.细胞。生物化学。 88：315-322，2003。 (C) 2002 Wiley-Liss, Inc.
Evidence suggests that vitamin D may have a protective role for prostate cancer. 1alpha,25-Dihydroxyvitamin D [1alpha,25(OH)(2)D] inhibits growth and induces differentiation of prostate cells. 25-Hydroxyvitamin D-1alpha-hydroxylase [1alpha-OHase], the enzyme that is responsible for the synthesis of 1alpha,25(OH)(2)D, is expressed in cultured prostate cells. We observed a marked decrease in 1alpha-OHase activity in prostate cancer cells, suggesting some defect of the 1alpha-OHase in these cells. To investigate whether the defect was due to dysregulation of the enzyme at the promoter level, a series of deletion constructs of the promoter was synthesized and incorporated upstream into the luciferase reporter gene. Two regions were identified with high basal activity in transfected normal prostate cell line (PZHPV-7),-1100 bp (AN2), and -394 bp (AN5) upstream of ATG start site of the 1alpha-OHase gene. When the reporter gene with either AN2 or AN5 was transfected into prostate cancer cell lines, we observed a lower basal promoter activity in PC-3 cells and DU145 cells than that found in PZHPV-7 cells for both constructs, and a loss of promoter activity in LNCaP cells. Thus, the results suggest that the defect in enzyme activity may result from the decreased promoter activity in prostate cancer cells. J. Cell. Biochem. 88: 315-322,2003. (C) 2002 Wiley-Liss, Inc.