PPARδ is an APC-regulated target of nonsteroidal anti-inflammatory drugs
PPARδ is an APC-regulated target of nonsteroidal anti-inflammatory drugs
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DOI：
10.1016/s0092-8674(00)81664-5
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发表时间：
1999-10-29
期刊：
影响因子：
64.5
通讯作者：
Kinzler, KW
中科院分区：
文献类型：
--
作者：
He, TC;Chan, TA;Kinzler, KW
通过分析人结直肠癌（CRC）细胞中的全局基因表达谱，将PPAR δ鉴定为APC的靶点。CRC中的PPAR δ表达升高，而CRC细胞中的APC则抑制了其表达。这种抑制是由PPAR δ启动子中的β-连环蛋白/Tcf-4-应答元件介导的。PPARs结合类花生酸的能力表明，PPARs δ可能是化学预防性非甾体抗炎药（NSAID）的靶点。含有PPAR δ-反应元件的报告基因被NSAID舒林酸抑制。此外，舒林酸能够破坏PPARdelta结合其识别序列的能力。这些发现表明NSAID通过抑制PPAR δ抑制肿瘤发生，该基因通常由APC调节。
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.