1alpha,25-Dihydroxyvitamin D3 down-regulates expression of prostate specific membrane antigen in prostate cancer cells

Prostate. 2008 May 15;68(7):773-83. doi: 10.1002/pros.20739.


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, 1alpha,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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Androgen Antagonists / pharmacology
  • Anilides / pharmacology
  • Antineoplastic Agents / pharmacology*
  • Biomarkers, Tumor
  • Calcitriol / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Drug Screening Assays, Antitumor
  • Gene Silencing
  • Humans
  • Male
  • Membrane Proteins / drug effects
  • Membrane Proteins / metabolism
  • Nitriles / pharmacology
  • Prostate-Specific Antigen / metabolism*
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / metabolism
  • RNA, Small Interfering / metabolism
  • Receptors, Androgen / drug effects
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism
  • Tosyl Compounds / pharmacology


  • Androgen Antagonists
  • Anilides
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Membrane Proteins
  • Nitriles
  • RNA, Small Interfering
  • Receptors, Androgen
  • Tosyl Compounds
  • bicalutamide
  • Prostate-Specific Antigen
  • Calcitriol