Open AccessThe drug resistance proteins, multidrug resistance‐associated protein and P‐glycoprotein, do not confer resistance to Fas‐induced cell death
Author(s) -
Cullen Karen,
Davey Ross,
Davey Mary
Publication year - 2001
Publication title -
cytometry
Language(s) - English
Resource type - Journals
eISSN - 1097-0320
pISSN - 0196-4763
DOI - 10.1002/1097-0320(20010301)43:3<189::aid-cyto1048>3.0.co;2-w
Subject(s) - p glycoprotein , multiple drug resistance , apoptosis , programmed cell death , biology , fas receptor , microbiology and biotechnology , flow cytometry , monoclonal antibody , drug resistance , western blot , cell culture , antibody , cancer research , immunology , biochemistry , gene , genetics
Background Multidrug resistance (MDR) is mediated by the drug resistance proteins, the multidrug resistance‐associated protein (MRP) and P‐glycoprotein, both of which confer resistance by the active efflux of chemotherapeutic drugs from the cell. Reduced Fas (CD95/APO‐1) expression and resistance to Fas‐mediated apoptosis have also been correlated with P‐glycoprotein–mediated MDR. Methods We investigated cell surface Fas expression (using anti‐Fas monoclonal antibody DX2.1) in a series of MRP‐expressing drug‐resistant leukemia sublines, and P‐glycoprotein–expressing leukemia sublines, and their susceptibility to apoptosis induced by anti‐Fas treatment (CH‐11 monoclonal antibody). Caspase‐3 activation was detected by Western blot and apoptosis was determined by flow cytometry with 7‐aminoactinomycin D (7‐AAD) staining of cells. Results Fas expression was not reduced in either the MRP‐ or P‐glycoprotein–expressing drug‐resistant cell lines, although expression was reduced by 15% in one low‐level drug‐resistant subline. Expression of MRP or P‐glycoprotein did not confer resistance to caspase‐3 activation or to anti–Fas‐induced cell death. Conclusions MDR mediated by the drug transport proteins MRP and P‐glycoprotein does not correlate with resistance to Fas‐mediated cell death or resistance to caspase‐3 activation. Cytometry 43:189–194, 2001. © 2001 Wiley‐Liss, Inc.