Characterization of an anthracycline-resistant human promyelocyte leukemia (HL-60) cell line with an elevated MDR-1 gene expression.
Multidrug resistance to a variety of cytotoxic drugs is due to decreased drug accumulation at the intracellular site of drug action. When due to increased energy-dependent drug efflux, this transport change is often associated with increased expression of an efflux pump for various lipophilic compounds, for example the P-glycoprotein which is the product of the MDR-1 gene. However, previously described HL-60 human promyelocytic leukemia cell lines resistant to the cytotoxic effect of anthracyclines have been reported not to express P-glycoprotein. We have isolated, by drug selection, an anthracycline-resistant HL-60 cell line that, in comparison to parental drug sensitive cells, exhibits a multidrug resistant phenotype including diminished intracellular drug retention, cross-resistance to multiple cytotoxic drugs, increased expression of a monoclonal antibody C219-reactive 180 kDa P-glycoprotein detected by Western blot analysis as well as increased expression of MDR-1 mRNA as determined by Northern blot and solution hybridization/RNAse protection analyses. Evidence is presented that the anthracycline-resistant HL-60 cells have amplified the MDR-1 gene.
Jönsson
K
K
Department of Medicine, Huddinge Hospital, Karolinska Institute, Sweden.
Dahlberg
N
N
Tidefelt
U
U
Paul
C
C
Andersson
G
G
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D001692:Biological Transport; D002469:Cell Separation; D004317:Doxorubicin / Q000378:metabolism / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000235:genetics*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D012333:RNA, Messenger; D004317:Doxorubicin