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(1-6). 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.