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Androgen receptor signaling and vitamin D receptor action in prostate cancer cells

Shalini Murthy1, Irina U Agoulnik, Nancy L Weigel

  • 1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas77030, USA.

The Prostate
|March 9, 2005
PubMed
Abstract

Insights

Vitamin D3 inhibits prostate cancer cell growth, but this effect is partly reversed by anti-androgens in some cell lines. However, vitamin D3 remains effective against most prostate cancers, even with androgen ablation therapy.

Area of Science:

  • Oncology
  • Endocrinology
  • Molecular Biology

Background:

  • 1,25(OH)2D3 inhibits prostate cancer cell growth.
  • Previous studies suggest 1,25(OH)2D3 actions in LNCaP cells are androgen-dependent.
  • Anti-androgen therapy is used for metastatic prostate cancer.

Purpose of the Study:

  • To assess the requirement for endogenous androgens in 1,25(OH)2D3-mediated growth inhibition of AR+ prostate cancer cell lines.
  • To investigate the mechanism of anti-androgen reversal of 1,25(OH)2D3-dependent growth inhibition in LNCaP cells.

Main Methods:

  • Assessed androgen requirement for 1,25(OH)2D3 growth inhibition in AR+ prostate cancer cell lines.
  • Investigated mechanism of anti-androgen reversal of 1,25(OH)2D3-dependent growth inhibition.
  • Analyzed AS3 (APRIN) gene as a potential common target.

Main Results:

  • 1,25(OH)2D3 inhibited androgen-independent LNCaP cell derivatives, but Casodex reduced this response.
  • AS3 (APRIN), a gene crucial for androgen-dependent growth arrest, is a primary target for both 1,25(OH)2D3 and androgens.
  • Casodex reduced AS3 induction by 1,25(OH)2D3, suggesting a role in the observed effect.
  • Casodex reversal of 1,25(OH)2D3 effects was unique to LNCaP-derived cells.

Conclusions:

  • Anti-androgen reversal of 1,25(OH)2D3-dependent growth inhibition is specific to LNCaP-derived prostate cancer cell lines.
  • 1,25(OH)2D3 strongly inhibits androgen-independent LNCaP cell derivatives.
  • VDR agonist treatment is likely effective in most prostate cancers, irrespective of androgen ablation therapy.

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