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Una pantalla genética para los candidatos a supresores de tumores identifica REST
Thomas F Westbrook1, Eric S Martin, Michael R Schlabach
1Howard Hughes Medical Institute, Department of Genetics, Harvard Partners Center for Genetics and Genomics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
Los investigadores identificaron REST/NRSF como un nuevo gen supresor de tumores. La pérdida de REST promueve el cáncer al aumentar la señalización PI(3)K, ofreciendo nuevas vías para el descubrimiento de genes de cáncer.
Área de la Ciencia:
- Biología del cáncer Biología del cáncer.
- Oncología Molecular Oncología Molecular
- Genética La genética.
Sus antecedentes:
- La tumorigénesis implica cambios genéticos y epigenéticos complejos.
- La identificación de genes clave que impulsan la transformación maligna es crucial para la investigación del cáncer.
Objetivo del estudio:
- Para identificar los genes que suprimen la transformación maligna en las células epiteliales mamarias humanas utilizando una pantalla de RNAi.
- Investigar el papel de REST/NRSF en el desarrollo del cáncer.
Principales métodos:
- Prueba genética basada en la interferencia de ARN (RNAi) para los supresores de transformación.
- Array híbridación genómica comparativa (Array-CGH) para las alteraciones genéticas.
- Análisis de mutación en células de cáncer colorrectal.
Principales resultados:
- Se identificaron supresores de tumores conocidos (TGFBR2, PTEN) y un nuevo supresor, REST/NRSF.
- Se encontraron deleciones de REST en el cáncer colorrectal y una mutación transformadora de REST.
- Se ha demostrado que las células deficientes en REST dependen de la señalización PI ((3) K para la transformación.
Conclusiones:
- REST funciona como un supresor de tumores humano, no reconocido previamente.
- La pérdida de REST contribuye al cáncer a través de la activación de la vía PI(3)K.
- Este estudio proporciona un método para descubrir nuevos genes que suprimen el cáncer.
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