Reed Karen R, Sansom Owen J, Hayes Anthony J, Gescher Andreas J, Winton Douglas J, Peters Jeffrey M, Clarke Alan R
Cardiff School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF103US, UK.
Oncogene. 2004 Nov 25;23(55):8992-6. doi: 10.1038/sj.onc.1208143.
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 ApcMinPPARdelta-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.
基于最近有关过氧化物酶体增殖物激活受体δ（PPARδ）激活促进肿瘤发生的报道，我们研究了该蛋白在Apc介导的肠道肿瘤发生中的作用。我们证明，成年小肠中Apc的失活虽然导致β-连环蛋白预期的核内积累，但并未导致PPARδ mRNA或蛋白预期的增加，相反，PPARδ mRNA和蛋白的水平降低。此外，我们发现ApcMinPPARδ基因敲除小鼠表现出更高的肠道肿瘤发生易感性。我们的数据表明，PPARδ不受β-连环蛋白的直接调控，抑制PPARδ活性不太可能是肠道恶性肿瘤化学预防或化疗的合适策略。
