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Genetic deficiency in Pparg does not alter development of experimental prostate cancer

Enrique Saez1, Peter Olson, Ronald M Evans

  • 1The Salk Institute for Biological Studies and Howard Hughes Medical Institute, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.

Nature Medicine
|September 10, 2003
PubMed

Insights

Peroxisome proliferator-activated receptor gamma (PPAR-gamma) does not appear to suppress prostate cancer. Research using mouse models found neither PPAR-gamma nor PPAR-alpha gene alterations affected tumor development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-gamma) has a debated role in cancer.
  • Loss-of-function mutations in PPARG found in colon and prostate tumors suggest it may be a tumor suppressor.
  • This study investigates the tumor suppressor hypothesis of PPAR-gamma in prostate cancer.

Purpose of the Study:

  • To determine if PPAR-gamma acts as a tumor suppressor in prostate cancer.
  • To evaluate the impact of PPARG and PPARA gene alterations on prostate cancer development.

Main Methods:

  • Utilized a genetically engineered mouse model for prostate cancer.
  • Assessed the effect of hemizygous deletion of the Pparg gene.
  • Examined the impact of complete ablation of the Ppara gene.

Main Results:

  • Hemizygous deletion of Pparg did not influence prostate cancer development in mice.
  • Complete ablation of Ppara also had no effect on prostate cancer progression in this model.
  • These findings challenge the notion of PPAR-gamma as a prostate tumor suppressor.

Conclusions:

  • PPAR-gamma does not function as a tumor suppressor in the context of prostate cancer studied.
  • PPAR-alpha also does not play a significant role in prostate cancer development in this experimental system.
  • Further research is needed to fully elucidate the role of nuclear receptors in cancer.

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