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Las frecuentes deleciones somáticas en el marco activan gp130 en tumores inflamatorios hepatocelulares
Sandra Rebouissou1, Mohamed Amessou, Gabrielle Couchy
1Inserm, U674, Génomique fonctionnelle des tumeurs solides, Paris F-75010, France.
Nature
|November 21, 2008
Resumen
Las mutaciones de ganancia de función en el gen IL6ST, que codifica para gp130, activan la señalización de la interleucina-6 (IL-6) en los tumores hepáticos. Estas mutaciones explican las vías inflamatorias y sugieren roles en otros cánceres epiteliales.
Área de la Ciencia:
- Hepatología Hepatología.
- Biología Molecular Biología Molecular
- Oncología Oncología.
Sus antecedentes:
- Los adenomas hepatocelulares inflamatorios (IHCA) son tumores benignos del hígado caracterizados por la inflamación.
- Se observa una mayor expresión de proteínas inflamatorias en los hepatocitos IHCA.
Objetivo del estudio:
- Para investigar los mecanismos moleculares que impulsan el IHCA.
- Para identificar las alteraciones genéticas responsables de la activación de la vía IL-6 en IHCA.
Principales métodos:
- Secuenciación genética de genes candidatos en muestras de IHCA.
- La expresión in vitro de los mutantes gp130 en las células hepatocelulares.
- Análisis de las alteraciones de gp130 y beta-catenina en los carcinomas hepatocelulares.
Principales resultados:
- Se identificaron mutaciones somáticas de ganancia de función en IL6ST (código gp130) en el 60% de los IHCA.
- El mutante gp130 activó la señalización STAT3 independientemente de la IL-6.
- gp130 alteraciones en los carcinomas hepatocelulares co-ocurridos con mutaciones de beta-catenina.
Conclusiones:
- Las mutaciones recurrentes de gp130 explican completamente la activación de la vía IL-6 en IHCA.
- Estos hallazgos sugieren un papel para las mutaciones gp130 en la conversión maligna de los hepatocitos.
- Alteraciones similares de gp130 pueden estar implicadas en otros tumores epiteliales inflamatorios con activación de STAT3.
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