Repression of β-catenin function in malignant cells by nonsteroidal antiinflammatory drugs | Zendy

Desheng Lu | Zendy; Howard B. Cottam | Zendy; Maripat Corr | Zendy; Dennis A. Carson | Zendy

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Repression of β-catenin function in malignant cells by nonsteroidal antiinflammatory drugs

Author(s) -

Desheng Lu,

Howard B. Cottam,

Maripat Corr,

Dennis A. Carson

Publication year - 2005

Publication title -

proceedings of the national academy of sciences

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 5.011

H-Index - 771

eISSN - 1091-6490

pISSN - 0027-8424

DOI - 10.1073/pnas.0509316102

Subject(s) - psychological repression , nonsteroidal , receptor , catenin , wnt signaling pathway , retinoid x receptor , peroxisome proliferator activated receptor , cancer research , retinoid , chemistry , nuclear receptor , mechanism of action , pharmacology , cyclooxygenase , function (biology) , transcription factor , microbiology and biotechnology , biology , biochemistry , signal transduction , enzyme , gene expression , retinoic acid , gene , in vitro

Activation of the Wnt/beta-catenin pathway promotes the development of several cancers and is an attractive target for chemopreventive and chemotherapeutic agents. Nonsteroidal antiinflammatory drugs (NSAIDs) have been reported to antagonize beta-catenin function, but their mechanism of action is not known. We demonstrate here that interference with beta-catenin function by NSAIDs does not correlate with cyclooxygenase (COX) inhibition. Instead, NSAID inhibition of beta-catenin requires the high level expression of peroxisome proliferator-activated receptor gamma (PPAR-gamma) and its co-receptor retinoid-X-receptor alpha (RXR-alpha). Immunoprecipitation experiments show that beta-catenin interacts with RXR-alpha and PPAR-gamma in some malignant cells. Repression of beta-catenin-dependent transcription by NSAIDs is thus indirect and depends on the coexpression of other nuclear receptors.

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