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Published on: March 28, 2013

New target genes for the peroxisome proliferator-activated receptor-γ (PPARγ) antitumour activity: Perspectives from

Daniela P Foti1, Francesco Paonessa, Eusebio Chiefari

  • 1Department of Clinical and Experimental Medicine "G. Salvatore", University of Catanzaro "Magna Graecia", V.le Europa (Loc. Germaneto), 88100 Catanzaro, Italy.

PPAR Research
|July 10, 2009
PubMed

Insights

Peroxisome proliferator-activated receptor gamma (PPARγ) agonists inhibit the insulin receptor (IR) through novel mechanisms. This suggests PPARγ agonists may be effective antiproliferative agents for cancers overexpressing the insulin receptor.

Area of Science:

  • Molecular Endocrinology
  • Cancer Biology
  • Oncology

Background:

  • The insulin receptor (IR) is vital for insulin's metabolic and proliferative effects.
  • Dysregulation of IR expression and function is linked to cancer development and progression, particularly in breast cancer.
  • Peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor involved in cell survival and proliferation, with known antineoplastic effects.

Purpose of the Study:

  • To investigate the relationship between PPARγ and the insulin receptor (IR) in cancer.
  • To explore the potential of PPARγ agonists as antiproliferative agents in IR-overexpressing tumors.

Main Methods:

  • Investigated the non-canonical, DNA-independent mechanisms by which PPARγ and its agonists affect IR gene transcription.
  • Evaluated the inhibitory effects of PPARγ activation on IR.

Main Results:

  • Demonstrated that PPARγ and its agonists inhibit the insulin receptor (IR).
  • Identified novel, non-canonical, DNA-independent mechanisms underlying this inhibition.
  • Established the insulin receptor (IR) as a new target gene for PPARγ.

Conclusions:

  • The insulin receptor (IR) is a novel target gene of PPARγ.
  • PPARγ agonists show potential as antiproliferative agents for neoplastic tissues that overexpress the insulin receptor (IR).

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