PPARdelta是非类固醇抗炎药物的APC调节的标
T C He1, T A Chan, B Vogelstein
1Johns Hopkins Oncology Center, Johns Hopkins University, Baltimore, Maryland 21231, USA.
Cell
|November 11, 1999
概括
瘤抑制剂APC通常在结直肠癌 (CRC) 中抑制PPARdelta. 像苏林达克这样的非类固醇抗炎药物 (NSAIDs) 抑制了这个基因,可能会阻止CRC瘤的生长.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 遗传学 是一个遗传学.
背景情况:
- 大肠直肠癌 (CRC) 是一个重大的健康问题.
- 大肠杆菌腺瘤多发症 (APC) 基因在CRC发育中起着至关重要的作用.
- 过氧体增殖器激活受体 (PPARs) 参与细胞过程和癌症.
研究的目的:
- 在结直肠癌中研究APC和PPARdelta之间的关系.
- 探索PPARdelta作为非类固醇抗炎药物 (NSAIDs) 在CRC化疗预防中的目标的潜在作用.
主要方法:
- 全球基因表达在人类结肠直肠癌细胞中的分析.
- 使用报告测试分析PPARdelta促进剂活性.
- 评估苏林达克对PPARdelta活性和结合的影响.
主要成果:
- 确定PPARB是APC的目标,PPARdelta表达在CRC中升高,并被APC抑制.
- 在APC的PPARdelta抑制中介于PPARdelta促进体中的β-catenin/Tcf-4反应元件.
- 无 NSAID 抗胰岛素抑制了 PPARdelta 的活性,并破坏了其 DNA 的结合,这表明化学预防的机制.
结论:
- 在正常情况下,APC会调节结直肠癌细胞中的PPARdelta表达.
- 像苏林达克这样的NSAIDs通过向和抑制PPARdelta来抑制瘤发生.
- 这些发现突出了在CRC中NSAID介导的化学预防的新机制.
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