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Related Experiment Videos

Human multidrug-resistant cell lines: increased mdr1 expression can precede gene amplification.

D W Shen, A Fojo, J E Chin

    Science (New York, N.Y.)
    |May 2, 1986
    PubMed
    Summary

    Multidrug resistance in cancer chemotherapy is often linked to the multidrug resistance (mdr1) gene. Increased mdr1 messenger RNA (mRNA) expression and DNA amplification are key mechanisms driving this resistance in human cancer cells.

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    Area of Science:

    • Molecular Biology
    • Cancer Research
    • Genetics

    Background:

    • Simultaneous resistance to multiple drugs hinders effective cancer chemotherapy.
    • Multidrug resistance (MDR) is a significant clinical challenge.
    • The multidrug resistance locus (mdr1) is implicated in MDR.

    Purpose of the Study:

    • To investigate the role of mdr1 gene expression and amplification in MDR.
    • To understand the mechanisms underlying MDR development in human cancer cells.
    • To identify common pathways contributing to MDR across different cancer types.

    Main Methods:

    • Selection of human KB carcinoma cells with cytotoxic drugs (colchicine, vinblastine, Adriamycin).
    • Analysis of mdr1 gene amplification and mdr1 messenger RNA (mRNA) expression levels.

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  • Examination of MDR sublines from human leukemia and ovarian carcinoma.

    • Main Results:

    • Drug selection led to increased mdr1 mRNA expression, initially without DNA amplification.
    • Higher resistance levels correlated with simultaneous mdr1 mRNA elevation and gene amplification.
    • Increased mdr1 expression and amplification were observed in resistant human leukemia and ovarian carcinoma cells.

    Conclusions:

    • Elevated mdr1 mRNA expression is a common mechanism for MDR in human cancer cells.
    • Gene amplification of mdr1 may follow initial increases in mRNA expression during resistance development.
    • Understanding mdr1 activation is crucial for overcoming MDR in cancer treatment.