Carcinogenesis Advance Access published online on January 16, 2004
Carcinogenesis, doi:10.1093/carcin/bgh082
© 2004 by Oxford University Press
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MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
1 Section of Endocrinology, Diabetes and Nutrition, Boston University School of Medicine, Boston, Massachusetts, 02118
* Corresponding author. E-mail: taichen{at}bu.edu.
Received 1 October 2003
; revised 20 December 2003
; accepted 6 January 2004
The hormonal form of vitamin D, 1
Vitamin D, calcium, parathyroid hormone
The prostate 25-hydroxyvitamin D-1
-hydroxylase is not influenced by parathyroid hormone and calcium: implications for prostate cancer chemoprevention by vitamin D
2 Department of Cancer Biology, Comprehensive Cancer Center of Wake Forest University, Winston-Salem, North Carolina 27157
3 Department of Urology, University of Miami School of Medicine, Miami, Florida 33101
,25-dihydroxyvitamin D [1,25(OH)2D] promotes the differentiation and inhibits the proliferation, invasiveness and metastasis of prostate cells. However, 1,25(OH)2D is not suitable as a chemopreventive agent because its administration can cause hypercalcemia. Serum levels of 1,25(OH)2D are tightly regulated by the renal enzyme, 25-hydroxyvitamin D-1-hydroxylase [1-OHase], which synthesizes 1,25(OH)2D from the prohormone, 25-hydroxyvitamin D [25(OH)D]. Normal prostate epithelial cells in primary culture, as well as several prostate cancer cell lines, also express 1-OHase and synthesize the hormone intracellularly. We investigated the regulation of the prostate 1-OHase by the three most important regulators of the renal 1-OHase: calcium, 1,25(OH)2D, and parathyroid hormone (PTH). The 1-OHase activity in the primary cultures of prostate epithelial cells was inhibited by 1,25(OH)2D3 at 10 and 100 nM, whereas PTH at 10 and 100 nM had no significant effect. Calcium at 1.2 and 2.4 mM had no significant effect on the enzyme activity in the PZ-HPV-7 cell line, a prostate epithelial cell line derived from normal prostate tissue. Conversely, 1.2 or 2.4 mM calcium markedly inhibited 1-OHase activity in a human kidney cell line used as a positive control. Furthermore, PTH at 100 nM and calcium at 1.2 and 2.4 mM had no effect on the 1-OHase gene promoter activity in prostate cells, whereas the promoter activity was inhibited 48±5% by 100 nM 1,25(OH)2D3. Our findings suggest that, unlike the renal enzyme, the prostate 1 -OHase is largely unregulated by serum levels of PTH and calcium. These findings support the hypothesis that vitamin D or 25(OH)D may be useful as chemopreventive agents for prostate cancer because their administration should cause an increased synthesis of 1,25(OH)2D within prostate cells.
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