Activation of nuclear hormone receptor peroxisome proliferator-activated receptor-delta accelerates intestinal adenoma growth.
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.
Gupta
Rajnish A
RA
Department of Medicine, The Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-6838, USA.
Wang
Dingzhi
D
Katkuri
Sharada
S
Wang
Haibin
H
Dey
Sudhansu K
SK
DuBois
Raymond N
RN
D000236:Adenoma / Q000378:metabolism / Q000473:pathology*; D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D017491:Genes, APC; D006801:Humans; D007414:Intestinal Neoplasms / Q000378:metabolism / Q000473:pathology*; D007417:Intestinal Polyps / Q000378:metabolism / Q000473:pathology*; D008024:Ligands; D051379:Mice; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000378:metabolism*; D013844:Thiazoles / Q000378:metabolism / Q000494:pharmacology*; D014157:Transcription Factors / Q000819:agonists* / Q000378:metabolism*
D025601:Adenomatous Polyposis Coli Protein; C425931:GW 501516; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D014157:Transcription Factors