Abstract
Previous studies have reported that P-glycoprotein (P-gp), a transmembrane efflux pump involved in multidrug resistance (MDR), was overexpressed in the doxorubicin (Dox)-resistant human erythroleukemia cell line K562. Nevertheless, several results suggested that P-gp was not the only mechanism involved in these resistant cells. Sequential co-expression of other MDR-associated proteins was sometimes reported, as MDR-associated protein (MRP) and lung resistance protein (LRP), in different MDR cell lines. Thus, mRNA expression and stability of P-gp, MRP and LRP were analyzed, while their corresponding protein levels were quantified in correlation with functional assay, in the K562 cell line and two Dox-resistant variants (K562/R). Their P-gp content was in accordance with their degree of resistance, but not as much in the level of mRNA expression, suggesting a post-transcriptional regulation. On the other hand, MRP could play a minor role in MDR because of an unchanged expression in K562/R sublines. A surprising progressive disappearance of LRP in both resistant cells suggested that the original mechanism of drug redistribution may be operative, involving a negative role for LRP.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
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ATP-Binding Cassette Transporters / genetics*
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ATP-Binding Cassette Transporters / metabolism
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Antineoplastic Agents / toxicity*
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Blotting, Northern
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Blotting, Southern
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Blotting, Western
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DNA Primers / chemistry
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Doxorubicin / pharmacology*
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Drug Resistance, Multiple / genetics*
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Drug Resistance, Neoplasm
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Enzyme Stability / physiology*
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Flow Cytometry
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Gene Expression
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Genes, MDR / physiology
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Humans
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K562 Cells / drug effects*
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K562 Cells / metabolism
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Multidrug Resistance-Associated Proteins
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Neoplasm Proteins / genetics*
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Neoplasm Proteins / metabolism*
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RNA, Messenger / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Sequence Analysis, DNA
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Transcription, Genetic
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Tumor Cells, Cultured / drug effects
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Tumor Cells, Cultured / metabolism
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Vault Ribonucleoprotein Particles / genetics*
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Vault Ribonucleoprotein Particles / metabolism
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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Antineoplastic Agents
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DNA Primers
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Multidrug Resistance-Associated Proteins
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Neoplasm Proteins
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RNA, Messenger
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Vault Ribonucleoprotein Particles
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major vault protein
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Doxorubicin