Gardner Lawrence B, Corn Paul G
New York University School of Medicine and MD Anderson Cancer Center, USA.
Cell Cycle. 2008 Jul 1;7(13):1916-24. doi: 10.4161/cc.7.13.6203. Epub 2008 Apr 24.
Many tumors are hypoxic, and cells that are experimentally rendered hypoxic display a variety of phenotypes which allow them to adapt to the micro-environment. These phenotypes include a shift from aerobic to anaerobic metabolism, a diminution of reactive oxygen species, an arrest of proliferation, apoptosis, and a secretion of pro-angiogenic growth factors. Some of these hypoxic phenotypes are re-capitulated in normoxic tumor cells (e.g., an increase in anaerobic metabolism), and some tumors have undergone mutations that allow them to bypass the cell cycle arrest and apoptosis typically seen in hypoxic cells. Hypoxic regulation of gene expression is responsible for many hypoxia-induced phenotypes, and here we review a variety of mechanisms by which gene expression is altered in hypoxic cells. These include transcription by HIF-1, the hypoxia inducible transcription factor, and other hypoxia-inducible transcription factors, including ones generated by hypoxic activation of the integrated stress response. Recent data from our laboratory demonstrate that nonsense mediated RNA decay is also regulated in hypoxic cells and thus may play an important role in hypoxic gene regulation and hypoxic phenotypes.
许多肿瘤存在缺氧情况，通过实验诱导产生缺氧的细胞会表现出多种表型，使其能够适应微环境。这些表型包括从有氧代谢向无氧代谢的转变、活性氧的减少、增殖停滞、凋亡以及促血管生成生长因子的分泌。其中一些缺氧表型在常氧肿瘤细胞中也会重现（例如无氧代谢增加），并且一些肿瘤发生了突变，使其能够绕过通常在缺氧细胞中出现的细胞周期停滞和凋亡。基因表达的缺氧调节导致了许多缺氧诱导的表型，在此我们综述缺氧细胞中基因表达改变的多种机制。这些机制包括缺氧诱导转录因子HIF-1以及其他缺氧诱导转录因子的转录，其中包括整合应激反应的缺氧激活所产生的转录因子。我们实验室最近的数据表明，无义介导的RNA降解在缺氧细胞中也受到调节，因此可能在缺氧基因调节和缺氧表型中发挥重要作用。
