Abstract
Recent reports have correlated multidrug resistance (MDR) and P-glycoprotein expression with decreased Fas expression and resistance to Fas-mediated apoptosis. We report the MRP-overexpressing MDR subline CEM/E1000 has the same Fas expression (MFI 74.3 +/- 0.7) as the parental CCRF-CEM T-cell leukaemia cells (MFI 70.0 +/- 3.6; P>0.05), and that the level of apoptosis induced by anti-Fas antibody or drug was similar in both cell lines. Further the P-glycoprotein-expressing CEM/VLB(100) subline of the CCRF-CEM cells showed increased Fas expression (MFI 114.8 +/- 3.6; P<0.001) and no resistance to Fas-mediated apoptosis. This questions the hypothesis that selection of drug resistance results in resistance to Fas-mediated apoptosis, with important implications for the rational use of immunotherapy in the treatment of drug resistant cancer.
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / biosynthesis
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ATP-Binding Cassette Transporters / biosynthesis
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Antibodies, Monoclonal / immunology
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Antibodies, Monoclonal / pharmacology
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Antineoplastic Agents / toxicity
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Antineoplastic Agents, Phytogenic / toxicity
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Apoptosis / drug effects
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Apoptosis / physiology*
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Cisplatin / toxicity
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Drug Resistance, Multiple / physiology*
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Drug Resistance, Neoplasm
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Etoposide / toxicity
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Humans
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Immunoglobulin M / immunology
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Immunoglobulin M / pharmacology
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Leukemia, T-Cell / drug therapy
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Leukemia, T-Cell / metabolism
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Leukemia, T-Cell / pathology
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Multidrug Resistance-Associated Proteins
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Tumor Cells, Cultured
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fas Receptor / biosynthesis
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fas Receptor / immunology
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fas Receptor / physiology*
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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ATP-Binding Cassette Transporters
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Antibodies, Monoclonal
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Antineoplastic Agents
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Antineoplastic Agents, Phytogenic
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Immunoglobulin M
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Multidrug Resistance-Associated Proteins
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fas Receptor
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Etoposide
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Cisplatin