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.
Reed
Karen R
KR
Cardiff School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF103US, UK.
Sansom
Owen J
OJ
Hayes
Anthony J
AJ
Gescher
Andreas J
AJ
Winton
Douglas J
DJ
Peters
Jeffrey M
JM
Clarke
Alan R
AR
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