Cell transformation by the superoxide-generating oxidase Mox1

Young Ah Suh, Rebecca S. Arnold, Bernard Lassegue, Jing Shi, Xiangxi Xu, Dan Sorescu, Andrew B. Chung, Kathy K. Griendling, J. David Lambeth

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1217 Scopus citations

Abstract

Reactive oxygen species (ROS) generated in some non-phagocytic cells are implicated in mitogenic signalling and cancer. Many cancer cells show increased production of ROS, and normal cells exposed to hydrogen peroxide or superoxide show increased proliferation and express growth-related genes. ROS are generated in response to growth factors, and may affect cell growth, for example in vascular smooth-muscle cells. Increased ROS in Ras-transformed fibroblasts correlates with increased mitogenic rate. Here we describe the cloning of mox1, which encodes a homologue of the catalytic subunit of the superoxide-generating NADPH oxidase of phagocytes, 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.

Original languageEnglish (US)
Pages (from-to)79-82
Number of pages4
JournalNature
Volume401
Issue number6748
DOIs
StatePublished - Sep 2 1999
Externally publishedYes

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    Suh, Y. A., Arnold, R. S., Lassegue, B., Shi, J., Xu, X., Sorescu, D., Chung, A. B., Griendling, K. K., & Lambeth, J. D. (1999). Cell transformation by the superoxide-generating oxidase Mox1. Nature, 401(6748), 79-82. https://doi.org/10.1038/43459