An NAD(P)H oxidase regulates growth and transcription in melanoma cells

nant melanoma cells spontaneously generate reactive oxygen species (ROS) that promote constitutive activation of the transcription factor nuclear factor-B (NF-B). Although an-tioxidants and inhibitors of NAD(P)H oxidases significantly reduce constitutive NF-B activation and suppress cell pro-liferation (11), the nature of the enzyme responsible for ROS production in melanoma cells has not been determined. To address this issue, we now have characterized the source of ROS production in melanoma cells. We report that ROS are generated by isolated, cytosol-free melanoma plasma mem-branes, with inhibition by NAD(P)H oxidase inhibitors. The p22phox, gp91phox, and p67phox components of the human phagocyte NAD(P)H oxidase and the gp91phox homolog NOX4 were demonstrated in melanomas by RT-PCR and sequenc-ing, and protein product for both p22phox and gp91phox wa