Redox Regulation in Human Melanocytes and Melanoma

Abstract

totic phenotype in the transformed cell. This conceptual frameThe human melanocyte is continuously exposed to intrinsic and work offers testable steps to determine the role of redox extrinsic sources of reactive biochemical species, but is finely tuned via the intrinsic anti-oxidant and radical properties of alterations in the carcinogenic evolution, prevention and treatmelanin to suppress the build-up of an altered redox phenoment of melanoma and other diseases of the melanocyte. type. We propose that this control is lost during melanomageKey words: Transcription factor, NF-kB, AP-1, Reactive nesis and inappropriate redox-sensitive transcriptional factor oxygen species, Glutathione, Superoxide anion activations occur which result in enhancement of an anti-apopand glutathione (GSH), melanin as an anti-oxidant and cellular pro-oxidant, response of melanin to ultraviolet (UV) light, anti-oxidant levels and melanomagenesis, redox regulation of transcription factors, and a conceptual framework for the pathogenesis of melanoma based on altered redox control.In response to UV light an inflammatory response is generated involving the production of massive amounts of various cytokines and growth factors by keratinocytes, a vigorous inflammatory/immunologic host response, and in some cases angiogenesis. Each one of these responses generates or stimulates the production of reactive oxygen or nitrogen species. Additionally, UV light interacts directly with biochemical constituents of the melanocyte to generate intracellular reactive oxygen species (ROS), hydrogen peroxide and/or superoxide anion. The sum total of these alterations is that melanocytes are subjected to an panoply of redox changes with secondary effects on melanin synthesis and a variety of signaling cascades.We suggest that alterations in these processes are fundamentally involved in the pathogenesis of melanoma and perhaps other pathologic states. These observations encum-

DHCR24 gene expression is upregulated in melanoma metastases and associated to resistance to oxidative stress‐induced apoptosis

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BRAFE600 in benign and malignant human tumours

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