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

被引：1003

作者：

He, TC

Chan, TA

Vogelstein, B

Kinzler, KW ^{[1
]}

机构：

[1] Johns Hopkins Oncol Ctr, Baltimore, MD 21231 USA

[2] Johns Hopkins Univ, Howard Hughes Med Inst, Baltimore, MD 21231 USA

来源：

CELL | 1999年 / 99卷 / 03期

关键词：

D O I：

10.1016/S0092-8674(00)81664-5

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

PPAR delta was identified as a target of APC through the analysis of global gene expression profiles in human colorectal cancer (CRC) cells. PPAR delta 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 PPAR delta promotor. The ability of PPARs to bind eicosanoids suggested that PPAR delta might be a target of chemopreventive nonsteroidal anti-inflammatory drugs (NSAIDs). Reporters containing PPAR delta-responsive elements were repressed by the NSAID sulindac. Furthermore, sulindac was able to disrupt the ability of PPAR delta to bind its recognition sequences. These findings suggest that NSAIDs inhibit tumorigenesis through inhibition of PPAR delta, the gene for which is normally regulated by APC.

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收藏

页码：335 / 345

页数：11

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