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Amplification of DNA sequences in human multidrug-resistant KB carcinoma cells

A T Fojo, J Whang-Peng, M M Gottesman

    Proceedings of the National Academy of Sciences of the United States of America
    |November 1, 1985
    PubMed

    Insights

    Multidrug resistance in KB carcinoma cells involves DNA sequence amplification. Common amplified DNA sequences were found across cell lines resistant to different chemotherapy drugs, suggesting their role in multidrug resistance.

    Area of Science:

    • Molecular Biology
    • Cancer Research
    • Genetics

    Background:

    • Cancer cell lines can develop resistance to chemotherapy drugs.
    • Multidrug resistance (MDR) is a significant challenge in cancer treatment.
    • KB carcinoma cells are a model for studying drug resistance.

    Purpose of the Study:

    • To investigate the genetic basis of multidrug resistance in KB carcinoma cells.
    • To identify specific DNA alterations associated with resistance to colchicine, adriamycin, and vinblastine.
    • To explore the role of DNA sequence amplification in MDR.

    Main Methods:

    • Developing and characterizing four KB carcinoma cell lines with independent resistance to colchicine, adriamycin, or vinblastine.
    • Analyzing chromosomal spreads to identify double-minute chromosomes.
    • Employing in-gel renaturation techniques to detect DNA sequence amplification.
    • Using specific DNA probes to identify amplified sequences.

    Main Results:

    • All resistant cell lines exhibited cross-resistance to multiple drugs, including actinomycin D.
    • Double-minute chromosomes were observed in multidrug-resistant KB cell lines.
    • Common and cell line-specific amplified DNA sequences were identified.
    • A revertant cell line, regaining drug sensitivity, lost its amplified sequences.

    Conclusions:

    • DNA sequence amplification, particularly common amplified sequences, plays a crucial role in the development of multidrug resistance in KB carcinoma cells.
    • The identified amplified regions are strong candidates for mediating multiple drug resistance.
    • Understanding these genetic mechanisms can inform future therapeutic strategies against drug-resistant cancers.

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