Roles of NADPH Oxidase 5 and Dual Oxidase 2 in Cancer

我们的实验室已经完成了第一个全面的评估， NADPH氧化酶家族成员在人类肿瘤中的作用。我们发现NADPH氧化酶5（NOX 5） 在黑色素瘤和血液恶性肿瘤中;在各种 胃肠道恶性肿瘤。我们已经在黑素瘤中表达了这两种人类蛋白质， 胰腺肿瘤细胞模型系统，以了解其体外功能。NOX 5 已经发现过表达下调p27，改变细胞周期进程，并产生 在暴露于离子霉素后，细胞外产生大量的过氧化氢。Duox 2 已经发现过表达也导致改变的细胞周期进程， 细胞外活性氧代谢的程度，用干扰素γ诱导 其部分通过使Duox 2启动子脱甲基而起作用。这两种基因都可能 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，到目前为止还没有 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 expressed 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 altered cell cycle progression, a remarkable degree of extracellular reactive oxygen metabolism, to be inducible with interferon gamma which functions, in part, by demethylating 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.