Activation of nuclear hormone receptor peroxisome proliferator-activated receptor-delta accelerates intestinal adenoma growth

Nat Med. 2004 Mar;10(3):245-7. doi: 10.1038/nm993. Epub 2004 Feb 1.

Abstract

We treated Apc(min) mice, which are predisposed to intestinal polyposis, with a selective synthetic agonist of peroxisome proliferator-activated receptor-delta (PPAR-delta). Exposure of Apc(min) mice to the PPAR-delta ligand GW501516 resulted in a significant increase in the number and size of intestinal polyps. The most prominent effect was on polyp size; mice treated with the PPAR-delta activator had a fivefold increase in the number of polyps larger than 2 mm. Our results implicate PPAR-delta in the regulation of intestinal adenoma growth.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoma / metabolism
  • Adenoma / pathology*
  • Adenomatous Polyposis Coli Protein / metabolism
  • Animals
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Genes, APC
  • Humans
  • Intestinal Neoplasms / metabolism
  • Intestinal Neoplasms / pathology*
  • Intestinal Polyps / metabolism
  • Intestinal Polyps / pathology*
  • Ligands
  • Mice
  • Receptors, Cytoplasmic and Nuclear / agonists*
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Thiazoles / metabolism
  • Thiazoles / pharmacology*
  • Transcription Factors / agonists*
  • Transcription Factors / metabolism*

Substances

  • Adenomatous Polyposis Coli Protein
  • GW 501516
  • Ligands
  • Receptors, Cytoplasmic and Nuclear
  • Thiazoles
  • Transcription Factors