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La sobreexpresión de un gen transportador en una línea celular de cáncer de pulmón humano multirresistente a los
S P Cole1, G Bhardwaj, J H Gerlach
1Cancer Research Laboratories, Queen's University, Kingston, Ontario, Canada.
Science (New York, N.Y.)
|December 4, 1992
Resumen
Las células de cáncer de pulmón resistentes a la quimioterapia sobreexpresan un nuevo transportador de cassette de unión al ATP. La amplificación génica en el cromosoma 16 se correlaciona con esta sobreexpresión y resistencia a los medicamentos, ofreciendo nuevos objetivos terapéuticos.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Genética La genética.
- Investigación de Investigación del Cáncer.
Sus antecedentes:
- Las células de cáncer de pulmón H69AR seleccionadas por la doxorubicina muestran resistencia a múltiples agentes quimioterapéuticos.
- Esta resistencia no está mediada por la glicoproteína P, un transportador común de resistencia a múltiples fármacos.
- Comprender los nuevos mecanismos de resistencia es crucial para desarrollar terapias efectivas contra el cáncer de pulmón.
Objetivo del estudio:
- Identificar y caracterizar nuevos genes y mecanismos que confieren resistencia a múltiples fármacos en el cáncer de pulmón.
- Para investigar la base genética de la resistencia a los medicamentos en la línea celular H69AR.
Principales métodos:
- Aislamiento de clones de ADN complementario (ADNc) correspondientes a ARN mensajeros sobreexpresados (ARNm) en las células H69AR.
- Análisis de los niveles de expresión de ARNm utilizando técnicas de hibridación.
- Análisis de amplificación génica a través del mapeo cromosómico (cromosoma 16, banda p13.1).
- Correlación de la amplificación génica y la expresión de ARNm con la sensibilidad a fármacos.
Principales resultados:
- Se descubrió que un nuevo ARNm (7.88.2 kilobases) estaba entre 100 y 200 veces sobreexpresado en las células H69AR en comparación con las células H69 parentales.
- Esta sobreexpresión se relacionó con la amplificación del gen congénito en el cromosoma 16 en la banda p13.1.1.
- La reversión a la sensibilidad al fármaco se correlacionó con la disminución de la expresión del ARNm y la pérdida de la amplificación génica.
- El ARNm identificado codifica un miembro de la superfamilia de transportadores transmembrana de la cassette de unión al ATP (ABC).
Conclusiones:
- Un nuevo transportador de cassette de unión de ATP, sobreexpresado debido a la amplificación génica en el cromosoma 16, contribuye a la resistencia a múltiples fármacos en el cáncer de pulmón.
- Este hallazgo proporciona un nuevo objetivo molecular para superar la resistencia a la quimioterapia en el cáncer de pulmón.
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