Characterization of a K562 multidrug-resistant cell line.
A daunorubicin-resistant variant of the K562 human leukemia cell line (K562-R), which demonstrates cross-resistance to other anthracycline antibiotics and Vinca alkaloids, has been developed in vitro by continuous exposure to daunorubicin. Cross-resistance to anthracyclines and Vinca alkaloids is reversed when cells are exposed to drugs in the presence of verapamil, a calcium channel blocker. The K562-R cell line overexpresses a 4.5-kilobase mRNA, which is thought to code for the Mr 170,000 membrane glycoprotein associated with multidrug resistance. Transport studies indicate reduced intracellular accumulation and retention of daunorubicin in the K562-R cells as compared to the parent cell line. These studies further suggest the presence of distinct cellular pools composed of both rapidly and slowly exchanging drug, with the rapidly exchanging pool being more pronounced in the resistant line. The development of multidrug resistance in the K562-R cell line is also associated with the overexpression of five different cell surface membrane proteins ranging in molecular weight between 50,000 and 210,000, whose function remains to be defined.
Yanovich
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Department of Medicine, Medical College of Virginia, Richmond 23298.
Hall
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Gewirtz
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DA
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003630:Daunorubicin / Q000037:antagonists & inhibitors / Q000378:metabolism; D004351:Drug Resistance / Q000235:genetics; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000032:analysis; D008565:Membrane Proteins / Q000032:analysis; D008970:Molecular Weight; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000911:Antibodies, Monoclonal; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D014700:Verapamil; D003630:Daunorubicin