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Increased ROS levels contribute to elevated transcription factor and MAP kinase activities in malignantly progressed mouse keratinocyte cell lines.
Gupta, A; Rosenberger, S F; Bowden, G T.
Afiliação
  • Gupta A; Department of Radiation Oncology, The University of Arizona Health Sciences Center, 1501 North Campbell Avenue, Tucson, AZ 85724, USA.
Carcinogenesis ; 20(11): 2063-73, 1999 Nov.
Article em En | MEDLINE | ID: mdl-10545407
There is evidence that reactive oxygen species (ROS) are important mediators of tumor promotion and progression. The molecular mechanisms involved in ROS-mediated signaling, however, are unclear at present. Using ionizing radiation and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) as model physical and chemical carcinogens, we have malignantly progressed 308 cells, a papilloma-producing mouse keratinocyte cell line, and investigated the molecular alterations in the progressed phenotypes. In this study, we demonstrate that both MNNG and radiation-progressed malignant variants showed elevated ROS levels that contributed to their proliferative capacity in vitro as well as in vivo. We found increased Erk-1/2 and p38 MAP kinase activities to be important components of ROS-mediated signaling. The pro-oxidant state also contributed to constitutive elevation of AP-1, NFkappaB and cAMP response element transactivation in the malignant phenotype. Our data provide evidence for a functional role of elevated ROS levels in tumor progression and implicate Erk-1/2 and p38 MAP kinase activation in the malignant progression of mouse keratinocytes.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Queratinócitos / Espécies Reativas de Oxigênio / Proteínas Quinases Ativadas por Mitógeno Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Carcinogenesis Ano de publicação: 1999 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Reino Unido
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Queratinócitos / Espécies Reativas de Oxigênio / Proteínas Quinases Ativadas por Mitógeno Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Carcinogenesis Ano de publicação: 1999 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Reino Unido