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

被引：68

作者：

Lu, DS ^{[1
]}

Cottam, HB

Corr, M

Carson, DA

机构：

[1] Univ Calif San Diego, Rebecca & John Moores Canc Ctr, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Div Rheumatol Allergy & Immunol, La Jolla, CA 92093 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2005年 / 102卷 / 51期

关键词：

peroxisome proliferator-activated receptor gamma; retinoid X receptor alpha;

D O I：

10.1073/pnas.0509316102

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Activation of the Wnt/beta-catenin pathway promotes the development of several cancers and is an attractive target for chemopreventive and chemotherapeutic agents. Nonsteroidal anti-inflammatory 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 p-catenin requires the high level expression of peroxisome proliferator-activated receptor gamma (PPAR-gamma) and its co-receptor retinoid-X-receptor alpha (RXR-alpha). Immunciprecipitation experiments show that beta-catenin interacts with RXR-a 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.

引用

页码：18567 / 18571

页数：5

共 58 条

[1] GASTROINTESTINAL DAMAGE ASSOCIATED WITH THE USE OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS [J].

ALLISON, MC ;

HOWATSON, AG ;

TORRANCE, CJ ;

LEE, FD ;

RUSSELL, RI .

NEW ENGLAND JOURNAL OF MEDICINE, 1992, 327 (11) :749-754

[2]

[Anonymous], 1993, AM J MED, DOI DOI 10.1016/0002-9343(93)90396-7

[3] EVALUATION OF THE STEREOSELECTIVE METABOLISM OF THE CHIRAL ANALGESIC DRUG ETODOLAC BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY [J].

BECKERSCHARFENKAMP, U ;

BLASCHKE, G .

JOURNAL OF CHROMATOGRAPHY-BIOMEDICAL APPLICATIONS, 1993, 621 (02) :199-207

[4] Sulindac targets nuclear β-catenin accumulation and Wnt signalling in adenomas of patients with familial adenomatous polyposis and in human colorectal cancer cell lines [J].

Boon, EMJ ;

Keller, JJ ;

Wormhoudt, TAM ;

Giardiello, FM ;

Offerhaus, GJA ;

van der Neut, R ;

Pals, ST .

BRITISH JOURNAL OF CANCER, 2004, 90 (01) :224-229

[5] Inhibition of β-catenin translocation in rodent colorectal tumors -: A novel explanation for the protective effect of nonsteroidal antiinflammatory drugs in colorectal cancer [J].

Brown, WA ;

Skinner, SA ;

Vogiagis, D ;

O'Brien, PE .

DIGESTIVE DISEASES AND SCIENCES, 2001, 46 (11) :2314-2321

[6] β-Catenin signaling in prostate cancer:: an early perspective [J].

Chesire, DR ;

Isaacs, WB .

[7] In vitro evidence for complex modes of nuclear β-catenin signaling during prostate growth and tumorigenesis [J].

Chesire, DR ;

Ewing, CM ;

Gage, WR ;

Isaacs, WB .

ONCOGENE, 2002, 21 (17) :2679-2694

[8] Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription [J].

Coghlan, MP ;

Culbert, AA ;

Cross, DAE ;

Corcoran, SL ;

Yates, JW ;

Pearce, NJ ;

Rausch, OL ;

Murphy, GJ ;

Carter, PS ;

Cox, LR ;

Mills, D ;

Brown, MJ ;

Haigh, D ;

Ward, RW ;

Smith, DG ;

Murray, KJ ;

Reith, AD ;

Holder, JC .

CHEMISTRY & BIOLOGY, 2000, 7 (10) :793-803

[9] Colorectal cancer prevention by non-steroidal anti-inflammatory drugs: effects of dosage and timing [J].

Collet, JP ;

Sharpe, C ;

Belzile, E ;

Boivin, JF ;

Hanley, J ;

Abenhaim, L .

BRITISH JOURNAL OF CANCER, 1999, 81 (01) :62-68

[10] RESOLUTION OF ETODOLAC AND ANTI-INFLAMMATORY AND PROSTAGLANDIN SYNTHETASE INHIBITING PROPERTIES OF THE ENANTIOMERS [J].

DEMERSON, CA ;

HUMBER, LG ;

ABRAHAM, NA ;

SCHILLING, G ;

MARTEL, RR ;

PACEASCIAK, C .

JOURNAL OF MEDICINAL CHEMISTRY, 1983, 26 (12) :1778-1780

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