title: Hormonal Regulation of the Repair of UV Photoproducts in Melanocytes by the Melanocortin Signaling Axis.
abstract: Melanoma is the deadliest form of skin cancer because of its propensity to spread beyond the primary site of disease and because it resists many forms of treatment. Incidence of melanoma has been increasing for decades. Although ultraviolet radiation (UV) has been identified as the most important environmental causative factor for melanoma development, UV-protective strategies have had limited efficacy in melanoma prevention. UV mutational burden correlates with melanoma development and tumor progression, underscoring the importance of UV in melanomagenesis. However, besides amount of UV exposure, melanocyte UV mutational load is influenced by the robustness of nucleotide excision repair, the genome maintenance pathway charged with removing UV photoproducts before they cause permanent mutations in the genome. In this review, we highlight the importance of the melanocortin hormonal signaling axis on regulating efficiency of nucleotide excision repair in melanocytes. By understanding the molecular mechanisms by which nucleotide excision repair can be increased, it may be possible to prevent many cases of melanoma by reducing UV mutational burden over time.
authors.affiliation: Markey Cancer Center, University of Kentucky College of Medicine, Lexington, KY.
authors.forename: Stuart G
authors.initials: SG
authors.lastname: Jarrett
authors.affiliation: Markey Cancer Center, University of Kentucky College of Medicine, Lexington, KY.|Department of Toxicology and Cancer Biology, University of Kentucky College of Medicine, Lexington, KY.|Department of Physiology, University of Kentucky College of Medicine, Lexington, KY.|Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY.|Department of Pediatrics, University of Kentucky College of Medicine, Lexington, KY.
authors.forename: John A
authors.initials: JA
authors.lastname: D'Orazio
mesh_terms: D000242:Cyclic AMP / Q000378:metabolism; D004260:DNA Repair; D006801:Humans; D053486:Melanocortins / Q000378:metabolism*; D008544:Melanocytes / Q000378:metabolism*; D008545:Melanoma / Q000453:epidemiology; D011740:Pyrimidine Dimers / Q000378:metabolism*; D044102:Receptor, Melanocortin, Type 1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D014466:Ultraviolet Rays / Q000009:adverse effects*; D014481:United States / Q000453:epidemiology; D014983:Xeroderma Pigmentosum / Q000209:etiology
chemical_list: D053486:Melanocortins; D011740:Pyrimidine Dimers; D044102:Receptor, Melanocortin, Type 1; D000242:Cyclic AMP