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Distinct thresholds govern Myc's biological output in vivo.
Murphy, Daniel J; Junttila, Melissa R; Pouyet, Laurent; Karnezis, Anthony; Shchors, Ksenya; Bui, Duyen A; Brown-Swigart, Lamorna; Johnson, Leisa; Evan, Gerard I.
Afiliación
  • Murphy DJ; Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
Cancer Cell ; 14(6): 447-57, 2008 Dec 09.
Article en En | MEDLINE | ID: mdl-19061836
Deregulated Myc triggers a variety of intrinsic tumor suppressor programs that serve to restrain Myc's oncogenic potential. Since Myc activity is also required for normal cell proliferation, activation of intrinsic tumor suppression must be triggered only when Myc signaling is oncogenic. However, how cells discriminate between normal and oncogenic Myc is unknown. Here we show that distinct threshold levels of Myc govern its output in vivo: low levels of deregulated Myc are competent to drive ectopic proliferation of somatic cells and oncogenesis, but activation of the apoptotic and ARF/p53 intrinsic tumor surveillance pathways requires Myc overexpression. The requirement to keep activated oncogenes at a low level to avoid engaging tumor suppression is likely an important selective pressure governing the early stages of tumor microevolution.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación Neoplásica de la Expresión Génica / Proteínas Proto-Oncogénicas c-myc / Neoplasias Límite: Animals / Humans Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2008 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación Neoplásica de la Expresión Génica / Proteínas Proto-Oncogénicas c-myc / Neoplasias Límite: Animals / Humans Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2008 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos