High SLC7A11 expression in normal skin of melanoma patients |
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| Affiliation: | 1. Department of Evolutionary Ecology, Doñana Biological Station, Consejo Superior de Investigaciones Científicas (CSIC), C/ Américo Vespucio 26, 41092 Sevilla, Spain;2. Laboratório de Genética, Instituto de Saúde Ambiental, Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, Edifício Egas Moniz, 1649-028 Lisboa, Portugal;3. Department of Dermatology, Virgen del Rocío University Hospital, Avda. Manuel Siurot s/n, 41013 Sevilla, Spain;1. Programa de Hematologia-Oncologia Pediátrica - PHOP, Instituto Nacional de Câncer José Alencar Gomes da Silva, Rio de Janeiro, Brazil;2. Divisão de Vigilância e Análise de Situação, Coordenação de Prevenção e Vigilância, Instituto Nacional de Câncer José Alencar Gomes da Silva, Rio de Janeiro, Brazil;3. Secretaria Estadual de Saúde da Paraíba, Registro de Câncer de Base Populacional de João Pessoa, Brazil;4. Secretaria Municipal de Saúde de Recife, Registro de Câncer de Base Populacional de Recife, Brazil;5. Secretaria de Saúde do Estado do Ceará, Registro de Câncer de Base Populacional de Fortaleza, Brazil;6. Secretaria Estadual de Saúde de Minas Gerais, Superintendência de Epidemiologia, Registro de Câncer de Base Populacional de Belo Horizonte, Brazil;7. Hospital de Câncer de Barretos, Fundação Pio XII, Registro de Câncer de Base Populacional de Barretos, Brazil;8. Coordenação Estadual de Atenção Oncológica, Secretaria Estadual de Saúde do Pará, Registro de Câncer de Base Populacional de Belém, Brazil;9. Secretaria Municipal de Saúde de Curitiba, Registro de Câncer de Base Populacional de Curitiba, Brazil;10. Secretaria Estadual de Saúde, Hospital Gov. João Alves Filho, Registro de Câncer de Base Populacional de Aracaju, Brazil;11. Fundação Centro de Controle de Oncologia, Registro de Câncer de Base Populacional de Manaus, Brazil;12. Associação de Combate ao Câncer de Goiás, Registro de Câncer de Base Populacional de Goiânia, Brazil;13. Secretaria Estadual de Saúde do Espírito Santo, Registro de Câncer de Base Populacional de Espírito Santo, Brazil;14. Faculdade de Saúde Pública da Universidade de São Paulo, Registro de Câncer de Base Populacional de São Paulo, Brazil;15. Secretaria Municipal de Saúde de Porto Alegre, Registro de Câncer de Base Populacional de Porto Alegre, Brazil;p. Secretaria de Estado de Saúde do Mato Grosso, Superintendência de Vigilância em Saúde, Registro de Câncer de Base Populacional de Cuiabá, Brazil;q. Fundação Hospital Amaral Carvalho, Registro de Câncer de Base Populacional de Jahu, Brazil;1. Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region, Nordre Fasanvej 57, 2000, Frederiksberg, Denmark;2. Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Bethesda, MD, 20892-9778, USA;3. Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark;1. Department of Surgery, Division of Urology, Center for Integrated Research on Cancer and Lifestyle, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA;2. Duke Cancer Institute, Duke University School of Medicine, Durham, NC, USA;3. Surgery Section, Durham VA Health Care System, Durham, NC, USA;4. Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA;5. Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA;6. Institute for Translational Epidemiology, and Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA;7. Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN, USA;1. Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China;2. Department of Medical Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & Affiliated Cancer Hospital of Nanjing Medical University, Nanjing China;3. State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210023, China;4. State Key Laboratory of Bioelectronics, Southeast University, Nanjing, China;1. Universidad de Las Palmas de Gran Canaria, Calle Juan de Quesada 30, 35001 Las Palmas de Gran Canaria, Spain;2. Dermatology Department, Hospital Universitario de Gran Canaria Doctor Negrín, Barranco de la Ballena s/n, 35010 Las Palmas de Gran Canaria, Spain;3. Research Unit, Hospital Universitario de Gran Canaria Doctor Negrín, Barranco de la Ballena s/n, 35010 Las Palmas de Gran Canaria, Spain;1. Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan;2. Division of Cancer Statistics Integration, Center for Cancer Control and Information Services, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan;3. Department of Global Health Policy, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan |
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| Abstract: | ![]()
BackgroundMelanoma is one of the highest metastatic cancers and its incidence is rapidly increasing. A great effort has been devoted to determine gene mutations and expression profiles in melanoma cells, but less attention has been given to the possible influence of melanin synthesis in melanocytes on melanomagenesis. SLC7A11 encodes the cystine/glutamate antiporter xCT and its expression increases the antioxidant capacity of cells by providing cysteine that may be used for glutathione (GSH) synthesis. Melanocytes, however, can also use cysteine for pheomelanin synthesis and pigmentation. Therefore, pheomelanin synthesis may lead to chronic oxidative stress. Possible consequences of this for melanomagenesis have never been explored.MethodsWe quantified the expression of SLC7A11 and other genes that are involved in the synthesis of pheomelanin but do not regulate the transport of cysteine from the extracellular medium to the cytosol (CTNS, MC1R, ASIP and SLC45A2) in non-tumorous skin of 45 patients of cutaneous melanoma and 50 healthy individuals. We controlled for the effects of Fitzpatrick skin type, age, gender, body mass, frequency of sun exposure and sunburns and number of melanocytic nevi, as well as for the intrinsic antioxidant capacity as given by the expression of the gene NFE2L2.ResultsThe expression of SLC7A11, but not of the other genes, was significantly higher in melanoma patients than in healthy individuals. This was independent of phenotypic factors and antioxidant capacity, thus supporting an effect of pheomelanin-induced oxidative stress on melanomagenesis.ConclusionOur findings indicate that SLC7A11 downregulation in normal epidermal melanocytes may represent a preventive treatment against melanoma. |
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| Keywords: | Gene expression Melanogenesis Melanoma Pheomelanin Oxidative stress Skin pigmentation |
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