[HTML][HTML] PPARδ is an APC-regulated target of nonsteroidal anti-inflammatory drugs

TC He, TA Chan, B Vogelstein, KW Kinzler - Cell, 1999 - cell.com
Cell, 1999cell.com
PPARδ was identified as a target of APC through the analysis of global gene expression
profiles in human colorectal cancer (CRC) cells. PPARδ expression was elevated in CRCs
and repressed by APC in CRC cells. This repression was mediated by β-catenin/Tcf-4-
responsive elements in the PPARδ promotor. The ability of PPARs to bind eicosanoids
suggested that PPARδ might be a target of chemopreventive nonsteroidal anti-inflammatory
drugs (NSAIDs). Reporters containing PPARδ-responsive elements were repressed by the …
Abstract
PPARδ was identified as a target of APC through the analysis of global gene expression profiles in human colorectal cancer (CRC) cells. PPARδ expression was elevated in CRCs and repressed by APC in CRC cells. This repression was mediated by β-catenin/Tcf-4-responsive elements in the PPARδ promotor. The ability of PPARs to bind eicosanoids suggested that PPARδ might be a target of chemopreventive nonsteroidal anti-inflammatory drugs (NSAIDs). Reporters containing PPARδ-responsive elements were repressed by the NSAID sulindac. Furthermore, sulindac was able to disrupt the ability of PPARδ to bind its recognition sequences. These findings suggest that NSAIDs inhibit tumorigenesis through inhibition of PPARδ, the gene for which is normally regulated by APC.
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