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Cell transformation by the superoxide-generating oxidase Mox1

Cell transformation by the superoxide-generating oxidase Mox1 Reactive oxygen species (ROS) generated in some non-phagocytic cells are implicated in mitogenic signalling and cancer 1,2,3,4,5,6 . Many cancer cells show increased production of ROS 7 , and normal cells exposed to hydrogen peroxide or superoxide show increased proliferation 8 and express growth-related genes 9,10,11 . ROS are generated in response to growth factors, and may affect cell growth 2,3,12,13 , for example in vascular smooth-muscle cells 6,13,14,15 . 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nature Springer Journals

Cell transformation by the superoxide-generating oxidase Mox1

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References (34)

Publisher
Springer Journals
Copyright
Copyright © 1999 by Macmillan Magazines Ltd.
Subject
Science, Humanities and Social Sciences, multidisciplinary; Science, Humanities and Social Sciences, multidisciplinary; Science, multidisciplinary
ISSN
0028-0836
eISSN
1476-4687
DOI
10.1038/43459
Publisher site
See Article on Publisher Site

Abstract

Reactive oxygen species (ROS) generated in some non-phagocytic cells are implicated in mitogenic signalling and cancer 1,2,3,4,5,6 . Many cancer cells show increased production of ROS 7 , and normal cells exposed to hydrogen peroxide or superoxide show increased proliferation 8 and express growth-related genes 9,10,11 . ROS are generated in response to growth factors, and may affect cell growth 2,3,12,13 , for example in vascular smooth-muscle cells 6,13,14,15 . 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.

Journal

Nature – Springer Journals

Published: Sep 2, 1999

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