Atypical multidrug resistance in CCRF-CEM cells selected for high level methotrexate resistance: reactivity to monoclonal antibody C219 in the absence of P-glycoprotein expression.
A series of CCRF-CEM sublines selected for extreme resistance to methotrexate has been shown previously to exhibit cross resistance to a number of agents belonging to the multidrug resistance phenotype (J.Natl.Cancer Inst.1989; 81, 1250-1254). The role of the mdr1 gene and its product (P-glycoprotein) in this atypical pattern of multidrug resistance has now been investigated. Southern and Northern analyses failed to demonstrate any amplification, rearrangement or over-expression of the mdr1 gene in the drug-resistant cells. Similarly, monoclonal antibodies MRK16 and JSB1 revealed no increase in the amount of P-glycoprotein present. By contrast, monoclonal antibody C219 detected a 170 kDa protein in all sublines, and in highest concentration in the most resistant cells. The results raise the possibility that a novel, C219-reactive protein may mediate resistance to both methotrexate and members of the multidrug resistance family.
Norris
M D
MD
Children's Leukaemia and Cancer Research Unit, Prince of Wales Children's Hospital, Sydney, Australia.
Haber
M
M
King
M
M
Davey
R A
RA
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D004247:DNA / Q000235:genetics; D004262:DNA Restriction Enzymes; D004351:Drug Resistance / Q000235:genetics*; D005434:Flow Cytometry; D005784:Gene Amplification; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics*; D008727:Methotrexate; D008970:Molecular Weight; D009693:Nucleic Acid Hybridization; D011506:Proteins / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D008562:Membrane Glycoproteins; D011506:Proteins; D012333:RNA, Messenger; D004247:DNA; D004262:DNA Restriction Enzymes; D008727:Methotrexate