Cell transformation by the superoxide-generating oxidase Mox1
Cell transformation by the superoxide-generating oxidase Mox1
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DOI：
10.1038/43459
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发表时间：
1999-09-02
期刊：
影响因子：
64.8
通讯作者：
Lambeth, JD
中科院分区：
文献类型：
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作者：
Suh, YA;Arnold, RS;Lambeth, JD
在一些非吞噬细胞中产生的活性氧（ROS）与有丝分裂信号传导和癌症有关（1-6）。许多癌细胞显示ROS7的产生增加，而暴露于过氧化氢或超氧化物的正常细胞显示增殖增加并表达生长相关基因（9-11）。ROS是根据生长因子产生的，并可能影响细胞生长（2,3,12,13），例如在血管平滑肌细胞中（6,13-15）。ras转化成纤维细胞中ROS的增加与有丝分裂率的增加相关（16）。在这里，我们描述了mox1的克隆，它编码吞噬细胞产生超氧化物NADPH氧化酶的催化亚基的同源物gp91phox（17,18）。mox1信使RNA在结肠、前列腺、子宫和血管平滑肌中表达，但在外周血白细胞中不表达。在平滑肌细胞中，血小板来源的生长因子诱导mox1 mRNA的产生，而反义mox1 mRNA则减少超氧化物的产生和血清刺激的生长。NIH3T3细胞中mox1的过表达增加了超氧化物的产生和细胞生长，表达mox1的细胞在胸腺小鼠中具有转化的外观，表现出不依赖锚定生长并产生肿瘤。这些数据将Mox1产生的ROS与非吞噬细胞的生长控制联系起来。
Reactive oxygen species (ROS) generated in some non-phagocytic cells are implicated in mitogenic signalling and cancer(1-6). Many cancer cells show increased production of ROS7, and normal cells exposed to hydrogen peroxide or superoxide show increased proliferations and express growth-related genes(9-11). ROS are generated in response to growth factors, and may affect cell growth(2,3,12,13), for example in vascular smooth-muscle cells(6,13-15) Increased ROS in Ras-transformed fibroblasts correlates with increased mitogenic rate(16). Here we describe the cloning of mox1, which encodes a homologue of the catalytic subunit of the superoxide-generating NADPH oxidase of phagocytes(17,18), gp91phox. mox1 messenger RNA is expressed in colon, prostate, uterus and vascular smooth muscle, but not in peripheral blood leukocytes. In smooth-muscle cells, platelet-derived growth factor induces mox1 mRNA production, while antisense mox1 mRNA decreases superoxide generation and serum-stimulated growth. Overexpression of mox1 in NIH3T3 cells increases superoxide generation and cell growth, Cells expressing mox1 have a transformed appearance, show,anchorage-independent growth and produce tumours in athymic mice. These data link ROS production by Mox1 to growth control in non-phagocytic cells.