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La expresión de la secuencia de codificación del sis/PDGF-2 humano normal induce la transformación celular.

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    El proto-oncogén del sistema humano, que codifica una cadena de factor de crecimiento derivado de plaquetas (PDGF, por sus siglas en inglés), adquiere actividad transformadora. La adición de un exón ascendente al clon c-sis 8 permitió la expresión de la proteína sis/PDGF-2 y la transformación celular.

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    Área de la Ciencia:

    • Biología Molecular Biología Molecular
    • Los oncogenes son oncogenes.
    • Transformación Celular Transformación Celular

    Sus antecedentes:

    • El sis proto-oncogén humano codifica una cadena polipeptídica de factor de crecimiento derivado de plaquetas (PDGF).
    • Se encontró que un clon específico de ADN humano (c-sis clon 8) que contiene secuencias relacionadas con v-sis era transcripcionalmente inactivo en las células NIH / 3T3.

    Objetivo del estudio:

    • Investigar el potencial transformador del proto-oncogén del sistema humano.
    • Identificar los elementos regulatorios necesarios para la expresión y la actividad biológica de sis/PDGF-2.

    Principales métodos:

    • Transfección de células NIH / 3T3 con clon c-sis 8 bajo control LTR retroviral.
    • Identificación de un exón ascendente putativo utilizando una sonda de transcripción relacionada con el sis.
    • Construcción y transfección de una molécula quimérica LTR-exon-c-sis clone 8.

    Principales resultados:

    • El clon 8 de c-sis por sí solo no mostró expresión detectable de la proteína sis/PDGF-2 ni actividad de transformación.
    • El exón ascendente identificado, cuando se inserta, confiere una alta actividad de transformación.
    • Las células transformadas expresaron productos traslacionales del sis humano/PDGF-2, lo que indica una activación funcional.

    Conclusiones:

    • La secuencia de codificación normal de un factor de crecimiento humano (sis/PDGF-2) posee un potencial transformador.
    • Elementos reguladores específicos, como el exón identificado aguas arriba, son cruciales para su expresión y actividad oncogénica.