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Cell transformation by the superoxide-generating oxidase Mox1

Abstract

Reactive oxygen species (ROS) generated in some non-phagocytic cells are implicated in mitogenic signalling and cancer1,2,3,4,5,6. Many cancer cells show increased production of ROS7, and normal cells exposed to hydrogen peroxide or superoxide show increased proliferation8 and express growth-related genes9,10,11. ROS are generated in response to growth factors, and may affect cell growth2,3,12,13, for example in vascular smooth-muscle cells6,13,14,15. Increased ROS in Ras-transformed fibroblasts correlates with increased mitogenic rate16. Here we describe the cloning of mox1, which encodes a homologue of the catalytic subunit of the superoxide-generating NADPH oxidase of phagocytes17,18, 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.

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Figure 1: Predicted amino-acid sequence of human Mox1 (GenBank accession no.
Figure 2: Expression of mox1 mRNA.
Figure 3: Superoxide generation by Mox1.
Figure 4: Properties of NIH 3T3 cells transfected with mox1.
Figure 5: Role of Mox1 in growth of vascular smooth-muscle cells.

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Acknowledgements

We thank D. Jones and D. Edmondson for discussions and technical advice; W. Sun for technical assistance; and D. Dillehay for the histological analysis. This work was supported by the NIH.

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Correspondence to J. David Lambeth.

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Suh, YA., Arnold, R., Lassegue, B. et al. Cell transformation by the superoxide-generating oxidase Mox1. Nature 401, 79–82 (1999). https://doi.org/10.1038/43459

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