1 Laboratory of Molecular Pharmacology of the Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, Maryland.
Antioxid Redox Signal. 2014 Jun 10;20(17):2873-89. doi: 10.1089/ars.2013.5603. Epub 2013 Oct 24.
Reactive oxygen species (ROS) promote genomic instability, altered signal transduction, and an environment that can sustain tumor formation and growth. The NOX family of NADPH oxidases, membrane-bound epithelial superoxide and hydrogen peroxide producers, plays a critical role in the maintenance of immune function, cell growth, and apoptosis. The impact of NOX enzymes in carcinogenesis is currently being defined and may directly link chronic inflammation and NOX ROS-mediated tumor formation.
Increased interest in the function of NOX enzymes in tumor biology has spurred a surge of investigative effort to understand the variability of NOX expression levels in tumors and the effect of NOX activity on tumor cell proliferation. These initial efforts have demonstrated a wide variance in NOX distribution and expression levels across numerous cancers as well as in common tumor cell lines, suggesting that much remains to be discovered about the unique role of NOX-related ROS production within each system. Progression from in vitro cell line studies toward in vivo tumor tissue screening and xenograft models has begun to provide evidence supporting the importance of NOX expression in carcinogenesis.
A lack of universally available, isoform-specific antibodies and animal tumor models of inducible knockout or over-expression of NOX isoforms has hindered progress toward the completion of in vivo studies.
In vivo validation experiments and the use of large, existing gene expression data sets should help define the best model systems for studying the NOX homologues in the context of cancer.
活性氧 (ROS) 促进基因组不稳定性、信号转导改变以及能够维持肿瘤形成和生长的环境。 NADPH 氧化酶家族的 NADPH 氧化酶，作为细胞膜结合的上皮超氧化物和过氧化氢的产生者，在维持免疫功能、细胞生长和细胞凋亡方面发挥着关键作用。NOX 酶在致癌作用中的影响目前正在被定义，并且可能直接将慢性炎症和 NOX ROS 介导的肿瘤形成联系起来。
对 NOX 酶在肿瘤生物学中的功能的兴趣增加，促使人们进行了大量的研究努力，以了解肿瘤中 NOX 表达水平的可变性以及 NOX 活性对肿瘤细胞增殖的影响。这些初步研究表明，NOX 在多种癌症和常见的肿瘤细胞系中的分布和表达水平存在很大差异，这表明，关于每个系统中与 NOX 相关的 ROS 产生的独特作用，还有很多有待发现。从体外细胞系研究向体内肿瘤组织筛选和异种移植模型的进展已经开始提供证据，支持 NOX 表达在致癌作用中的重要性。
缺乏普遍可用的、同工型特异性抗体和可诱导敲除或过表达 NOX 同工型的动物肿瘤模型，阻碍了体内研究的完成。
体内验证实验和利用大型现有基因表达数据集应该有助于确定研究癌症中 NOX 同源物的最佳模型系统。
