Sequential gene expression of P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP) and lung resistance protein: functional activity of P-gp and MRP present in the doxorubicin-resistant human K562 cell lines

Anticancer Drugs. 2001 Mar;12(3):247-58. doi: 10.1097/00001813-200103000-00010.


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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • ATP-Binding Cassette Transporters / genetics*
  • ATP-Binding Cassette Transporters / metabolism
  • Antineoplastic Agents / toxicity*
  • Blotting, Northern
  • Blotting, Southern
  • Blotting, Western
  • DNA Primers / chemistry
  • Doxorubicin / pharmacology*
  • Drug Resistance, Multiple / genetics*
  • Drug Resistance, Neoplasm
  • Enzyme Stability / physiology*
  • Flow Cytometry
  • Gene Expression
  • Genes, MDR / physiology
  • Humans
  • K562 Cells / drug effects*
  • K562 Cells / metabolism
  • Multidrug Resistance-Associated Proteins
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Transcription, Genetic
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / metabolism
  • Vault Ribonucleoprotein Particles / genetics*
  • Vault Ribonucleoprotein Particles / metabolism


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP-Binding Cassette Transporters
  • Antineoplastic Agents
  • DNA Primers
  • Multidrug Resistance-Associated Proteins
  • Neoplasm Proteins
  • RNA, Messenger
  • Vault Ribonucleoprotein Particles
  • major vault protein
  • Doxorubicin