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Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
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Peroxisome proliferator-activated receptor-gamma and growth inhibition by its ligands in prostate cancer

Daisuke Nagata1, Hashimoto Yoshihiro, Makoto Nakanishi

  • 1Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Japan.

Cancer Detection and Prevention
|September 16, 2008
PubMed
Abstract

Insights

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligands like 15d-PGJ2 and troglitazone inhibit prostate cancer cell growth and DNA synthesis. These PPAR-gamma ligands show potential as therapeutic agents for prostate cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is expressed in various human cancers.
  • PPAR-gamma activation by ligands can inhibit cancer cell growth and induce differentiation.
  • The exact mechanism of PPAR-gamma ligand anti-proliferative effects remains unclear.

Purpose of the Study:

  • To investigate PPAR-gamma expression in human prostate cancer.
  • To evaluate the impact of PPAR-gamma ligands (15d-PGJ2 and troglitazone) on prostate cancer cell proliferation.

Main Methods:

  • Examined PPAR-gamma expression in prostate cancer cell lines and tissues.
  • Assessed the effects of 15d-PGJ2 and troglitazone on prostate cancer cell proliferation and DNA synthesis.
  • Utilized prostate specific antigen (PSA) promoter reporter assays to analyze androgen-stimulated gene activity.

Main Results:

  • PPAR-gamma is frequently over-expressed in androgen-independent prostate cancer.
  • 15d-PGJ2 and troglitazone dose-dependently inhibited prostate cancer cell proliferation and DNA synthesis.
  • PPAR-gamma ligands suppressed androgen-stimulated PSA promoter activity and PSA protein expression without affecting androgen receptor (AR) expression.

Conclusions:

  • PPAR-gamma ligands demonstrate anti-proliferative effects on prostate cancer cells.
  • These findings suggest that PPAR-gamma ligands could be valuable therapeutic agents for prostate cancer.

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