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La NF-kappaB funciona como promotor tumoral en el cáncer asociado a la inflamación
Eli Pikarsky1, Rinnat M Porat, Ilan Stein
1Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel. peli@hadassah.org.il
Nature
|August 27, 2004
Resumen
La inflamación crónica contribuye al desarrollo del cáncer. La activación del factor nuclear kappaB (NF-kappaB) es crucial para la progresión del cáncer asociado a la inflamación, por lo que es un objetivo terapéutico potencial para la prevención.
Área de la Ciencia:
- Oncología Oncología.
- Inmunología Inmunología.
- Hepatología Hepatología.
Sus antecedentes:
- La inflamación crónica está relacionada con aproximadamente el 20% de los cánceres humanos, sin embargo, sus mecanismos siguen sin estar claros.
- La activación del factor nuclear kappaB (NF-kappaB) es una respuesta inflamatoria clave que a menudo se encuentra en los tumores.
- El papel de NF-kappaB en la vinculación de la inflamación con el cáncer requiere una mayor aclaración.
Objetivo del estudio:
- Para investigar el papel de NF-kappaB en el desarrollo de carcinoma hepatocelular asociado a la inflamación.
- Para determinar si NF-kappaB es un mediador crítico en la progresión de la hepatitis crónica al cáncer de hígado.
Principales métodos:
- Utilizó ratones Mdr2-knockout, un modelo para la hepatitis colestática espontánea y el carcinoma hepatocelular.
- Monitoreo de la hepatitis y la progresión del cáncer, evaluando la activación de NF-kappaB a través del factor de necrosis tumoral alfa (TNFalpha).
- Intervenido mediante la inhibición de NF-kappaB utilizando un transgén superrepresor de IkappaB inducible específico de hepatocitos y tratamiento anti-TNFalpha en diferentes etapas de la enfermedad.
Principales resultados:
- La activación de NF-kappaB en los hepatocitos fue desencadenada por la inflamación a través de TNFalpha.
- La inhibición temprana de NF-kappaB (desde el nacimiento hasta los 7 meses) no afectó la hepatitis ni la transformación temprana.
- La supresión de NF-kappaB en etapa tardía condujo a la apoptosis de los hepatocitos transformados y evitó el desarrollo de carcinoma hepatocelular.
Conclusiones:
- El NF-kappaB es esencial para la progresión del cáncer asociado a la inflamación.
- La orientación de NF-kappaB puede ofrecer una estrategia para la prevención del cáncer en enfermedades inflamatorias crónicas.
- El momento de la inhibición de NF-kappaB es crítico para la eficacia terapéutica en la prevención de la progresión tumoral.
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