Drug resistance does not correlate with resistance to Fas-mediated apoptosis.
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.
Cullen
K V
KV
Department of Cell and Molecular Biology, University of Technology, Sydney, Westbourne Street, Gore Hill, Sydney, NSW 2065, Australia.
Davey
R A
RA
Davey
M W
MW
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000633:toxicity; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002945:Cisplatin / Q000633:toxicity; D018432:Drug Resistance, Multiple / Q000502:physiology*; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000633:toxicity; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology / Q000494:pharmacology; D015458:Leukemia, T-Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D002945:Cisplatin; D005047:Etoposide; D007075:Immunoglobulin M; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D019014:fas Receptor