PPARδ status and Apc-mediated tumourigenesis in the mouse intestine
PPARδ status and Apc-mediated tumourigenesis in the mouse intestine
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DOI：
10.1038/sj.onc.1208143
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发表时间：
2004-11-25
期刊：
影响因子：
8
通讯作者：
Clarke, AR
中科院分区：
文献类型：
--
作者：
Reed, KR;Sansom, OJ;Clarke, AR
基于最近的报告，过氧化物酶体增殖物激活受体δ（PPARdelta）激活促进肿瘤发生，我们已经研究了这种蛋白在APC介导的肠道肿瘤发生的作用。我们证明，Apc在成人小肠中的失活，虽然引起预期的β-连环蛋白的核积累，但不会引起预期的PPARdelta mRNA或蛋白质的增加，相反，PPARdelta mRNA和蛋白质的水平降低。此外，我们发现Apc（Min）PPARdelta缺失小鼠表现出增加的肠道肿瘤发生倾向。我们的数据表明，PPARdelta不直接受β-连环蛋白的调节，并且PPARdelta活性的抑制不太可能是肠道恶性肿瘤的化学预防或化学治疗的适当策略。
Based on recent reports that peroxisome proliferator-activated receptor delta (PPARdelta) activation promotes tumourigenesis, we have investigated the role of this protein in Apc-mediated intestinal tumourigenesis. We demonstrate that the inactivation of Apc in the adult small intestine, while causing the expected nuclear accumulation of beta-catenin, does not cause the expected increase in PPARdelta mRNA or protein but conversely, the levels of PPARdelta mRNA and protein are lowered. Furthermore, we find that Apc(Min)PPARdelta-null mice exhibit an increased predisposition to intestinal tumourigenesis. Our data suggest that PPARdelta is not directly regulated by beta-catenin, and that inhibition of PPARdelta activity is unlikely to be an appropriate strategy for the chemoprevention or chemotherapy of intestinal malignancies.