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

Tong Chuan He, Timothy A. Chan, Bert Vogelstein, Kenneth W Kinzler

Research output: Contribution to journalArticle

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 PPARS-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.

Original languageEnglish (US)
Pages (from-to)335-345
Number of pages11
JournalCell
Volume99
Issue number3
DOIs
StatePublished - Oct 29 1999

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Peroxisome Proliferator-Activated Receptors
Anti-Inflammatory Agents
Pharmaceutical Preparations
Sulindac
Colorectal Neoplasms
Catenins
Eicosanoids
Transcriptome
Gene expression
Carcinogenesis
Genes
Cells

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

PPARδ is an APC-regulated target of nonsteroidal anti-inflammatory drugs. / He, Tong Chuan; Chan, Timothy A.; Vogelstein, Bert; Kinzler, Kenneth W.

In: Cell, Vol. 99, No. 3, 29.10.1999, p. 335-345.

Research output: Contribution to journalArticle

He, Tong Chuan ; Chan, Timothy A. ; Vogelstein, Bert ; Kinzler, Kenneth W. / PPARδ is an APC-regulated target of nonsteroidal anti-inflammatory drugs. In: Cell. 1999 ; Vol. 99, No. 3. pp. 335-345.
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