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ras gene Amplification and malignant transformation.

S Pulciani, E Santos, L K Long

    Molecular and Cellular Biology
    |October 1, 1985
    PubMed
    Summary
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    High levels of the human H-ras-1 proto-oncogene in NIH 3T3 cells cause morphologic transformation. Gene amplification of ras genes may also contribute to human cancer development.

    Area of Science:

    • Molecular Biology
    • Oncology
    • Cell Biology

    Background:

    • Proto-oncogenes, such as H-ras-1, play critical roles in cellular regulation.
    • Abnormalities in proto-oncogene expression or structure can lead to cellular transformation and cancer.

    Purpose of the Study:

    • To investigate the role of the human H-ras-1 proto-oncogene in the morphologic transformation of NIH 3T3 mouse cells.
    • To explore the potential involvement of ras gene amplification in human carcinomas.

    Main Methods:

    • Transfection of NIH 3T3 cells with recombinant DNA containing the human H-ras-1 proto-oncogene.
    • Analysis of H-ras-1 RNA and p21 protein expression levels in transformed cells.
    • Screening of human tumor biopsies for amplification of ras genes, specifically the K-ras-2 locus.

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    Main Results:

    • Transfection with large amounts of the H-ras-1 proto-oncogene induced morphologic transformation in NIH 3T3 cells.
    • Elevated H-ras-1 RNA and p21 expression correlated with the malignant properties of the transformed cells.
    • Amplification of the human K-ras-2 locus was detected in one out of 75 human lung carcinoma biopsies.

    Conclusions:

    • The transformation of NIH 3T3 cells is attributed to multiple copies of the H-ras-1 proto-oncogene, not spontaneous mutation.
    • Ras gene amplification represents an alternative mechanism by which ras genes can contribute to human neoplasia development.