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 language | English |
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Pages (from-to) | 241-6 |
Number of pages | 6 |
Journal | International Journal of Cancer |
Volume | 52 |
Issue number | 2 |
DOIs | |
Publication status | Published - 9 Sept 1992 |
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