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首页> 外文期刊>Cancer Cell >Recruitment of HIF-1alpha and HIF-2alpha to common target genes is differentially regulated in neuroblastoma: HIF-2alpha promotes an aggressive phenotype.
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Recruitment of HIF-1alpha and HIF-2alpha to common target genes is differentially regulated in neuroblastoma: HIF-2alpha promotes an aggressive phenotype.

机译：在成神经细胞瘤中，向共同靶基因募集HIF-1alpha和HIF-2alpha受到了不同的调节：HIF-2alpha促进了侵袭性表型。

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摘要

In neuroblastoma specimens, HIF-2alpha but not HIF-1alpha is strongly expressed in well-vascularized areas. In vitro, HIF-2alpha protein was stabilized at 5% O2 (resembling end capillary oxygen conditions) and, in contrast to the low HIF-1alpha activity at this oxygen level, actively transcribed genes like VEGF. Under hypoxia (1% O2), HIF-1alpha was transiently stabilized and primarily mediated acute responses, whereas HIF-2alpha protein gradually accumulated and governed prolonged hypoxic gene activation. Knockdown of HIF-2alpha reduced growth of neuroblastoma tumors in athymic mice. Furthermore, high HIF-2alpha protein levels were correlated with advanced clinical stage and high VEGF expression and predicted poor prognosis in a clinical neuroblastoma material. Our results demonstrate the relevance of HIF-2alpha in neuroblastoma progression and have general tumor biological implications.
机译：在成神经细胞瘤标本中，HIF-2alpha而非HIF-1alpha在血管良好的区域强烈表达。在体外，HIF-2alpha蛋白稳定在5％的O2下（类似于末端毛细管氧条件），并且与在该氧水平下低的HIF-1alpha活性相反，它积极转录了VEGF等基因。在缺氧（1％O2）下，HIF-1alpha暂时稳定并主要介导急性反应，而HIF-2alpha蛋白逐渐积累并控制长时间的缺氧基因激活。击倒HIF-2alpha减少了无胸腺小鼠中神经母细胞瘤肿瘤的生长。此外，高HIF-2alpha蛋白水平与晚期临床阶段和高VEGF表达相关，并预测临床神经母细胞瘤材料的不良预后。我们的结果证明了HIF-2alpha在神经母细胞瘤进展中的相关性，并具有一般的肿瘤生物学意义。

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