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Las mutaciones de ERF revelan un equilibrio de factores ETS que controlan la oncogénesis de la próstata

  • 0Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.
Nature +

|

15 de junio de 2017

|

15 de junio de 2017

Ver abstracta en PubMed

Resumen

Este resumen es generado por máquina.

Cáncer de próstata

Área De La Ciencia

  • Biología molecular
  • La genética
  • En el campo de la oncología

Sus Antecedentes

  • La fusión de genes TMPRSS2-ERG impulsa la mitad de los cánceres de próstata mediante la regulación al alza del factor de transcripción ERG.
  • Se observan mutaciones y deleciones recurrentes en ERF, un miembro de la familia ETS, en tumores de próstata.

Objetivo Del Estudio

  • Para investigar el papel de las mutaciones de ERF en el cáncer de próstata.
  • Aclarar la relación funcional entre ERG y ERF en el desarrollo y la progresión del cáncer de próstata.

Principales Métodos

  • Análisis de las mutaciones de ERF y su efecto en la estabilidad de las proteínas.
  • Estudios funcionales en células normales de próstata de ratón y líneas celulares de cáncer de próstata.
  • Immunoprecipitación de la cromatina seguida de secuenciación (ChIP-seq) para evaluar los sitios de unión de ERF y ERG.

Principales Resultados

  • Las mutaciones de ERF disminuyen la estabilidad de la proteína y están asociadas con tumores que carecen de regulación ERG al alza.
  • La pérdida de ERF imita los fenotipos de ganancia de función de ERG, incluida la expansión del receptor de andrógenos.
  • El ERG inhibe la unión del ERF al ADN, y el ERF puede contrarrestar la actividad oncogénica del ERG.

Conclusiones

  • La oncogenicidad de ERG implica la competencia y la inactivación del supresor tumoral ERF.
  • El ERF actúa como supresor tumoral, oponiéndose a las funciones oncogénicas del ERG.
  • Este modelo de competencia puede extenderse a otros factores de transcripción oncogénicos y supresores de tumores endógenos.

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