Roles of NADPH Oxidase 5 and Dual Oxidase 2 in Cancer

我们实验室已经完成了对NADPH氧化酶家族成员在人类肿瘤中存在的最早的全面评估之一。我们发现NADPH氧化酶5(NOX 5)在黑色素瘤和血液系统恶性病变中被发现；双重氧化酶2在各种胃肠道恶性肿瘤中被发现。我们已经在黑色素瘤和胰腺肿瘤细胞模型系统中过度暴露或上调了这两种人类蛋白的表达，以了解它们在体外的功能。研究发现，在暴露于离子霉素后，NOx 5过表达可下调p27，改变细胞周期进程，并产生相当数量的胞外过氧化氢。已发现DUOX 2过表达还导致显著程度的细胞外活性氧代谢，可被干扰素γ诱导，其作用部分是通过增强STAT 1与DUOX 2启动子的结合来实现的。这两种基因都可能在产生氧化剂“旁观者”效应方面发挥重要作用。我们的总体目标是了解这些氧化酶在人类癌症中的功能，到目前为止还没有详细探讨过。

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.