Shafee Norazizah, Kaluz Stefan, Ru Ning, Stanbridge Eric J
Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, Malaysia.
Cancer Lett. 2009 Sep 8;282(1):109-15. doi: 10.1016/j.canlet.2009.03.004. Epub 2009 Apr 1.
The phosphatidylinositol 3-kinase/Akt (PI3K) pathway regulates hypoxia-inducible factor (HIF) activity. Higher expression of HIF-1alpha and carbonic anhydrase IX (CAIX), a hypoxia-inducible gene, in HT10806TG fibrosarcoma cells (mutant N-ras allele), compared to derivative MCH603 cells (deleted mutant N-ras allele), correlated with increased PI3K activity. Constitutive activation of the PI3K pathway in MCH603/PI3K(act) cells increased HIF-1alpha but, surprisingly, decreased CAIX levels. The cell-type specific inhibitory effect on CAIX was confirmed at the transcriptional level whereas epigenetic modifications of CA9 were ruled out. In summary, our data do not substantiate the generalization that PI3K upregulation leads to increased HIF activity.
磷脂酰肌醇3激酶/蛋白激酶B（PI3K）信号通路调节缺氧诱导因子（HIF）的活性。与衍生的MCH603细胞（缺失突变型N-ras等位基因）相比，HT10806TG纤维肉瘤细胞（突变型N-ras等位基因）中HIF-1α和碳酸酐酶IX（CAIX，一种缺氧诱导基因）的高表达与PI3K活性增加相关。MCH603/PI3K(act)细胞中PI3K信号通路的组成性激活增加了HIF-1α，但令人惊讶的是，降低了CAIX水平。在转录水平证实了对CAIX的细胞类型特异性抑制作用，而排除了CA9的表观遗传修饰。总之，我们的数据并不支持PI3K上调导致HIF活性增加这一普遍观点。
