Iα,25-dihydroxyvitamin D3 down-regulates expression of prostate specific membrane antigen in prostate cancer cells

Rita E. Serda, Marco Bisoffi, Todd A. Thompson, Ming Ji, John L. Omdahl, Laurel O. Sillerud

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

BACKGROUND. Prostate specific membrane antigen (PSMA) expression correlates with prostate cancer grade and is increased in hormone-refractory prostate cancer. The increased expression of PSMA following androgen deprivation therapy may be a consequence of the down-regulation of PSMA expression by androgen. Moreover, 1α,25-dihydroxyvitamin D3 (1,25-VD) has been shown to suppress prostate cancer progression as well as cell motility and invasion. Since PSMA is positively correlated with both of these characteristics, we hypothesized that 1,25-VD would regulate PSMA expression. METHODS. LNCaP prostate cancer cells were treated with 1,25-VD, followed by analysis of cell surface PSMA expression. The PSMA enhancer, located within the third intron of the PSMA gene, was cloned into a reporter vector and regulation by 1,25-VD was investigated. The role of the androgen receptor (AR) in 1,25-VD mediated suppression of PSMA expression was examined using Casodex and AR specific siRNA. RESULTS. Surface expression of PSMA was significantly decreased in a dose-dependent manner by 10 nM 1,25-VD or greater. Regulation by 1,25-VD occurred at the level of the PSMA enhancer. Over-expression of the vitamin D receptor (VDR) also decreased expression of PSMA. Additionally, suppression of AR translation using siRNA technology blocked the suppressive effect of 1,25-VD on PSMA expression, however inhibition of PSMA expression by 1,25-VD occurred in the absence of androgens. CONCLUSIONS. Suppression of PSMA by 1,25-VD occurs at the level of the PSMA enhancer and is elevated by over-expression of the VDR. This regulation involves the AR, but is not dependent on the presence of androgens.

Original languageEnglish (US)
Pages (from-to)773-783
Number of pages11
JournalProstate
Volume68
Issue number7
DOIs
StatePublished - May 15 2008

Keywords

  • Androgen receptor
  • Prostate
  • PSMA
  • Vitamin D

ASJC Scopus subject areas

  • Urology

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