PPARdelta status and Apc-mediated tumourigenesis in the mouse intestine.
Based on recent reports that peroxisome proliferator-activated receptor delta (PPARdelta) activation promotes tumourigenesis, we have investigated the role of this protein in Apc-mediated intestinal tumourigenesis. We demonstrate that the inactivation of Apc in the adult small intestine, while causing the expected nuclear accumulation of beta-catenin, does not cause the expected increase in PPARdelta mRNA or protein but conversely, the levels of PPARdelta mRNA and protein are lowered. Furthermore, we find that ApcMinPPARdelta-null mice exhibit an increased predisposition to intestinal tumourigenesis. Our data suggest that PPARdelta is not directly regulated by beta-catenin, and that inhibition of PPARdelta activity is unlikely to be an appropriate strategy for the chemoprevention or chemotherapy of intestinal malignancies.
Cardiff School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF103US, UK.
Karen R
KR
Reed
Owen J
OJ
Sansom
Anthony J
AJ
Hayes
Andreas J
AJ
Gescher
Douglas J
DJ
Winton
Jeffrey M
JM
Peters
Alan R
AR
Clarke
D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism*; D000483:Alleles; D000818:Animals; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D007413:Intestinal Mucosa / Q000378:metabolism; D007414:Intestinal Neoplasms / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000378:metabolism; D009374:Neoplasms, Experimental; D047494:PPAR delta / Q000378:metabolism*; D048068:PPAR-beta / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D051176:beta Catenin
D025601:Adenomatous Polyposis Coli Protein; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D047494:PPAR delta; D048068:PPAR-beta; D015534:Trans-Activators; D051176:beta Catenin