The superoxide-generating oxidase Nox1 is functionally required for Ras oncogene transformation
The superoxide-generating oxidase Nox1 is functionally required for Ras oncogene transformation
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DOI：
10.1158/0008-5472.can-03-3909
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发表时间：
2004-05-15
期刊：
影响因子：
11.2
通讯作者：
Kamata, T
中科院分区：
文献类型：
--
作者：
Mitsushita, J;Lambeth, JD;Kamata, T
激活的Ras癌基因可以转化各种哺乳动物细胞，并与大量恶性人类肿瘤的发生有关。最近的研究表明，活性氧如超氧化物和H2O2的产生参与了激活的Ras细胞转化。然而，参与ras转化的氧化酶的性质目前尚不清楚。在这里，我们报道了Ras癌基因通过丝裂原激活的蛋白激酶激酶-丝裂原激活的蛋白激酶途径上调Nox1的表达，Nox1是产生超氧化物的NADPH氧化酶的催化亚基的同源物，并且设计了小干扰rna来靶向Nox1 mRNA，有效地阻断了Ras转化的表型，包括锚定非依赖性生长、形态改变和胸腺小鼠肿瘤的产生。因此，我们认为Ras诱导的Nox1增加活性氧的产生是致癌Ras转化所必需的。
The activated Ras oncogene can transform various mammalian cells and has been implicated in development of a high population of malignant human tumors. Recent studies suggest that generation of reactive oxygen species such as superoxide and H2O2 is involved in cell transformation by the activated Ras. However, the nature of an oxidase participating in Ras-transformation is presently unknown. Here, we report that Ras oncogene up-regulates the expression of Nox1, a homologue of the catalytic subunit of the superoxide-generating NADPH oxidase, via the mitogen-activated protein kinase kinase-mitogen-activated protein kinase pathway, and that small interfering RNAs designed to target Nox1 mRNA effectively blocks the Ras transformed phenotypes including anchorage-independent growth, morphological changes, and production of tumors in athymic mice. Therefore, we propose that increased reactive oxygen species generation by Ras-induced Nox1 is required for oncogenic Ras transformation.