Premium
Over‐expression of P‐glycoprotein and glutathione S‐transferase PI in MCF‐7 cells selected for vincristine resistance in vitro
Author(s) -
Whelan Richard D. H.,
Waring Clare J.,
Wolf C. Roland,
Hayes John D.,
Hosking Louise K.,
Hill Bridget T.
Publication year - 1992
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910520215
Subject(s) - mcf 7 , p glycoprotein , biology , glutathione , microbiology and biotechnology , isozyme , cell culture , cisplatin , vincristine , cytotoxicity , in vitro , biochemistry , enzyme , chemotherapy , multiple drug resistance , genetics , human breast , cancer cell , cancer , cyclophosphamide , antibiotics
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 μM) 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 applification. 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. © 1992 Wiley‐Liss, Inc.