期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 364, 期 1-2, 页码 54-64出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2012.08.007
关键词
Vitamin D receptor; Prostate; Metabolism; CYP3A4; CYP3A5
资金
- Prostate Cancer Charity (UK)
- Cancer Translational Research Group (Northern Ireland)
- BBSRC [BB/D523651/1] Funding Source: UKRI
- MRC [G0800247] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/D523651/1] Funding Source: researchfish
- Medical Research Council [G0800247] Funding Source: researchfish
- Prostate Cancer UK [PG09-26] Funding Source: researchfish
We investigated the capacity for vitamin D receptor (VDR) to modulate the expression of CYP3A4 and other genes that may facilitate the oxidative inactivation of androgens such as testosterone and androstanediol within prostate cells. We report that exposure to the active hormonal form of vitamin D markedly increased gene expression of CYP3A4 and CYP3A5 and ultimately achieved levels of intracellular CYP3A enzyme activity within LNCaP prostate cancer cells that were comparable to that observed for Caco2 cells, an established model of CYP3A induction, and resulted in the increased turnover of testosterone to its inactive 6 beta-OH metabolite. We demonstrate that VDR directs CYP3A4 and CYP3A5 expression through binding to distinct regulatory motifs located within the 5' promoter regions of both genes. The current data highlight the potential application of VDR-based treatment regimes as a means to limit the bioavailability of growth-promoting androgens within the tumor microenvironment. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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