Kamat Chandrashekhar D, Green Dixy E, Warnke Linda, Thorpe Jessica E, Ceriello Antonio, Ihnat Michael A
Department of Cell Biology, University of Oklahoma Health Sciences Center, 726 BMSB, 940 S.L. Young Boulevard, Oklahoma City, OK, USA.
Cancer Lett. 2007 May 8;249(2):209-19. doi: 10.1016/j.canlet.2006.08.017. Epub 2006 Sep 25.
There is much controversy in the literature regarding the role of p53 status response on hypoxia inducible factor (HIF) signaling in response to chronic relative hypoxia (CRH). The goal of this paper was to methodically examine this response in isogenically matched tumor cells. We report that p53-mutant (MUT) cells, versus p53-wild-type (WT) cells, showed decreased apoptosis, increased cell proliferation with higher basal HIF-1alpha levels in response to CRH. In addition, we found increased HIF-mediated transactivation and increased VEGF release with decreased HIF-1alpha/p53 and HIF-1alpha/MDM-2 partnering in p53-MUT versus p53-WT cells in response to CRH.
关于p53状态反应在慢性相对缺氧（CRH）反应中对缺氧诱导因子（HIF）信号传导的作用，文献中存在很多争议。本文的目的是系统地研究同基因匹配的肿瘤细胞中的这种反应。我们报告，与p53野生型（WT）细胞相比，p53突变型（MUT）细胞在CRH反应中显示出凋亡减少、细胞增殖增加以及基础HIF-1α水平升高。此外，我们发现，在CRH反应中，与p53-WT细胞相比，p53-MUT细胞中HIF介导的反式激活增加、VEGF释放增加，而HIF-1α/p53和HIF-1α/MDM-2的结合减少。
