Prostatic 25‐hydroxyvitamin D‐1α‐hydroxylase and its implication in prostate cancer
- 6 January 2003
- journal article
- research article
- Published by Wiley in Journal of Cellular Biochemistry
- Vol. 88 (2), 315-322
- https://doi.org/10.1002/jcb.10342
Abstract
Evidence suggests that vitamin D may have a protective role for prostate cancer. 1α,25‐Dihydroxyvitamin D [1α,25(OH)2D] inhibits growth and induces differentiation of prostate cells. 25‐Hydroxyvitamin D‐1α‐hydroxylase [1α‐OHase], the enzyme that is responsible for the synthesis of 1α,25(OH)2D, is expressed in cultured prostate cells. We observed a marked decrease in 1α‐OHase activity in prostate cancer cells, suggesting some defect of the 1α‐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 1α‐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.Keywords
Funding Information
- The Commonwealth of Massachusetts (4118PP1017, 41211159016)
- US Army (DAMD17-01-1-0025)
This publication has 16 references indexed in Scilit:
- 25-Hydroxyvitamin D-1α-hydroxylase activity is diminished in human prostate cancer cells and is enhanced by gene transferThe Journal of Steroid Biochemistry and Molecular Biology, 2002
- Molecular cloning, characterization, and promoter analysis of the human 25-hydroxyvitamin D3-1α-hydroxylase geneProceedings of the National Academy of Sciences, 1999
- TREATMENT OF EARLY RECURRENT PROSTATE CANCER WITH 1,25-DIHYDROXYVITAMIN D3 (CALCITRIOL)Journal of Urology, 1998
- Parathyroid hormone activation of the 25-hydroxyvitamin D 3 -1α-hydroxylase gene promoterProceedings of the National Academy of Sciences, 1998
- Cloning of Human 25-Hydroxyvitamin D-1 -Hydroxylase and Mutations Causing Vitamin D-Dependent Rickets Type 1Molecular Endocrinology, 1997
- The 25-Hydroxyvitamin D 1-Alpha-Hydroxylase Gene Maps to the Pseudovitamin D-Deficiency Rickets (PDDR) Disease LocusJournal of Bone and Mineral Research, 1997
- 25-Hydroxyvitamin D 3 1α-Hydroxylase and Vitamin D SynthesisScience, 1997
- Phase II trial of oral 1,25-dihydroxyvitamin D (calcitriol) in hormone refractory prostate cancerUrologic Oncology: Seminars and Original Investigations, 1995
- The Antiproliferative and Differentiative Activities of 1,25-Dihydroxyvitamin D3 Are Potentiated by Epidermal Growth Factor and Attenuated by Insulin in Cultured Human KeratinocytesJournal of Investigative Dermatology, 1995
- Neonatal human foreskin keratinocytes produce 1,25-dihydroxyvitamin D3Biochemistry, 1986