PPARdelta is an APC-regulated target of nonsteroidal anti-inflammatory drugs.
PPARdelta is an APC-regulated target of nonsteroidal anti-inflammatory drugs.
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发表时间：
1999
期刊：
影响因子：
64.5
通讯作者：
T. He;T. Chan;B. Vogelstein;K. Kinzler
中科院分区：
文献类型：
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作者：
T. He;T. Chan;B. Vogelstein;K. Kinzler
通过分析人结直肠癌 (CRC) 细胞的全局基因表达谱，将 PPARB 确定为 APC 的靶标。 PPARδ 表达在 CRC 中升高，并在 CRC 细胞中被 APC 抑制。这种抑制是由 PPARδ 启动子中的 β-catenin/Tcf-4 反应元件介导的。 PPAR 结合类二十烷酸的能力表明 PPARδ 可能是化学预防性非甾体抗炎药 (NSAID) 的靶标。含有 PPARδ 反应元件的报告分子受到 NSAID 舒林酸的抑制。此外，舒林酸能够破坏 PPARδ 结合其识别序列的能力。这些发现表明 NSAIDs 通过抑制 PPARδ 来抑制肿瘤发生，PPARδ 基因通常由 APC 调节。
PPARB was identified as a target of APC through the analysis of global gene expression profiles in human colorectal cancer (CRC) cells. PPARdelta 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 PPARdelta promotor. The ability of PPARs to bind eicosanoids suggested that PPARdelta might be a target of chemopreventive non-steroidal anti-inflammatory drugs (NSAIDs). Reporters containing PPARdelta-responsive elements were repressed by the NSAID sulindac. Furthermore, sulindac was able to disrupt the ability of PPARdelta to bind its recognition sequences. These findings suggest that NSAIDs inhibit tumorigenesis through inhibition of PPARdelta, the gene for which is normally regulated by APC.