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Expression of the normal human sis/PDGF-2 coding sequence induces cellular transformation.

A Gazit, H Igarashi, I M Chiu

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    This summary is machine-generated.

    The human sis proto-oncogene, encoding a platelet-derived growth factor (PDGF) chain, gains transforming activity. Adding an upstream exon to c-sis clone 8 enabled sis/PDGF-2 protein expression and cellular transformation.

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    Area of Science:

    • Molecular Biology
    • Oncogenes
    • Cellular Transformation

    Background:

    • The human sis proto-oncogene encodes a polypeptide chain of platelet-derived growth factor (PDGF).
    • A specific human DNA clone (c-sis clone 8) containing v-sis-related sequences was found to be transcriptionally inactive in NIH/3T3 cells.

    Purpose of the Study:

    • To investigate the transforming potential of the human sis proto-oncogene.
    • To identify regulatory elements necessary for sis/PDGF-2 expression and biological activity.

    Main Methods:

    • Transfection of NIH/3T3 cells with c-sis clone 8 under retroviral LTR control.
    • Identification of a putative upstream exon using a sis-related transcript probe.
    • Construction and transfection of a chimeric LTR-exon-c-sis clone 8 molecule.

    Main Results:

    • c-sis clone 8 alone showed no detectable sis/PDGF-2 protein expression or transforming activity.
    • The identified upstream exon, when inserted, conferred high-titer transforming activity.
    • Transformed cells expressed human sis/PDGF-2 translational products, indicating functional activation.

    Conclusions:

    • The normal coding sequence of a human growth factor (sis/PDGF-2) possesses transforming potential.
    • Specific regulatory elements, like the identified upstream exon, are crucial for its expression and oncogenic activity.