Roles of NADPH Oxidase 5 and Dual Oxidase 2 in Cancer

我们的实验室已经完成了对人类肿瘤中NADPH氧化酶家族成员存在的第一次全面评估。我们发现NADPH氧化酶5（NOX 5）在黑色素瘤和血液系统恶性肿瘤中发现;双氧化酶2在各种胃肠道恶性肿瘤中发现。我们在黑色素瘤和胰腺肿瘤细胞模型系统中过度暴露或上调这两种人类蛋白质的表达，以了解它们的体外功能。已经发现NOX 5过表达下调p27，改变细胞周期进程，并在暴露于离子霉素后产生大量的细胞外过氧化氢。已经发现Duox 2过表达也导致显著程度的细胞外活性氧代谢，其可被干扰素γ诱导，干扰素γ部分地通过增强stat 1与duox 2启动子的结合而起作用。这两个基因可能在产生氧化剂“旁观者”效应中起重要作用。我们的总体目标是了解这些氧化酶在人类癌症中的功能，迄今为止尚未详细探索。

Our laboratory has completed one of the first comprehensive evaluations of the presence of NADPH oxidase family members in human tumors. We found that NADPH oxidase 5 (NOX 5)is found in melanomas and in hematologic malingancies; dual oxidase 2 is found in various gastrointestinal malignancies. We have either over-exposed or upregulated the expression of both of these human proteins in melanoma and pancreatic tumor cell model systems to understand their functions in vitro. NOX 5 overexpression has been found to downregulate p27, alter cell cycle progression, and generate considerable amounts of extracellular hydrogen peroxide after exposure to ionomycin. Duox 2 overexpression has been found to also lead to a remarkable degree of extracellular reactive oxygen metabolism, to be inducible with interferon gamma which functions, in part, by enhancing stat 1 binding to the duox 2 promoter. Both of these genes may play an important role in producing an oxidant "bystander" effect. Our overall goal is to understand the function of these oxidases in human cancer, which, to date has not been explored in detail.