PPARdelta is an APC-regulated target of nonsteroidal anti-inflammatory drugs.
Journal:
Cell 1999 OctAuthors:
He TC, Chan TA, Vogelstein B, Kinzler KW
Abstract
PPARB was identified as a target of APC through the analysis of global gene expression profiles in human colorectal cancer (CRC) cells. PPARdelta expression was elevated in CRCs and repressed by APC in CRC cells. This repression was mediated by beta-catenin/Tcf-4-responsive elements in the PPARdelta promotor. The ability of PPARs to bind eicosanoids suggested that PPARdelta might be a target of chemopreventive non-steroidal anti-inflammatory drugs (NSAIDs). Reporters containing PPARdelta-respons
...[more]ive elements were repressed by the NSAID sulindac. Furthermore, sulindac was able to disrupt the ability of PPARdelta to bind its recognition sequences. These findings suggest that NSAIDs inhibit tumorigenesis through inhibition of PPARdelta, the gene for which is normally regulated by APC.[less]
Mesh Headings:
Adenomatous Polyposis Coli Protein, Anti-Inflammatory Agents, Non-Steroidal, Apoptosis, Colonic Neoplasms, Cytoskeletal Proteins, Gene Expression Regulation, Genes, APC, Humans, Receptors, Cytoplasmic and Nuclear, Sulindac, TCF Transcription Factors, Trans-Activators, Transcription Factor 7-Like 2 Protein, Transcription Factors, Tumor Cells, Cultured, beta Catenin