Over-expression of P-glycoprotein and glutathione S-transferase pi in MCF-7 cells selected for vincristine resistance in vitro

Richard D. H. Whelan, Clare J. Waring, C. Roland Wolf, John D. Hayes, Louise K. Hosking, Bridget T. Hill (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    42 Citations (Scopus)

    Abstract

    This study has provided evidence that exposure of the wild-type MCF-7 human breast carcinoma cell line to the mutagen ethyl methane sulphonate (EMS), followed by selection in vincristine (VCR), resulted in a stably-resistant subline, designated VCREMS, which expressed an approximately 14-fold level of resistance to VCR. This VCREMS subline showed cross-resistance (3-fold) to adriamycin (ADR) and to etoposide (3-fold), but not to cisplatin. The addition of a non-toxic concentration of verapamil (6.6 microM) significantly enhanced VCR cytotoxicity only in the resistant subline. This resistance was associated with over-expression of P-glycoprotein (Pgp), but without a concomitant increase in Pgp mRNA or gene amplification. In addition, activities of total glutathione S-transferases (GST) and glutathione peroxidase were elevated in this resistant subline, with over-expression of the GST-pi isozyme and its associated mRNA being identified, without gene amplification. This VCR-selected resistant MCF-7 cell line therefore provides another example of a breast carcinoma subline in which there is co-ordinate over-expression of both Pgp and GST-pi, without attributing a causal relationship to either event, and extends the range of anti-tumour drugs known to elicit modifications in glutathione metabolism.

    Original languageEnglish
    Pages (from-to)241-6
    Number of pages6
    JournalInternational Journal of Cancer
    Volume52
    Issue number2
    DOIs
    Publication statusPublished - 9 Sep 1992

      Fingerprint

    Keywords

    • ATP-Binding Cassette, Sub-Family B, Member 1
    • Breast Neoplasms/chemistry
    • Drug Resistance
    • Glutathione/analysis
    • Glutathione Reductase/analysis
    • Glutathione Transferase/analysis
    • Membrane Glycoproteins/analysis
    • RNA, Messenger/analysis
    • Tumor Cells, Cultured
    • Vincristine/metabolism

    Cite this