Document Detail

Expression of the multidrug resistance proteins MRP2 and MRP3 in human hepatocellular carcinoma.
MedLine Citation:
PMID:  11745434     Owner:  NLM     Status:  MEDLINE    
Treatment of hepatocellular carcinoma (HCC) by chemotherapy is often impeded by the intrinsic multidrug resistance (MDR) of this frequent primary cancer of the liver. The MDR phenotype can be caused by ATP-dependent export of chemotherapeutic drugs across the plasma membrane being mediated by transporters of the MDR P-glycoprotein family or of the multidrug resistance protein (MRP) family. To elucidate the role of MRP family members in HCC, we analyzed the expression and subcellular localization of MRP1 (ABCC1), MRP2 (ABCC2) and MRP3 (ABCC3); all 3 isoforms have been shown to confer resistance to chemotherapeutic drugs. Semiquantitative RT-PCR demonstrated that MRP2 and MRP3 mRNA expression in HCC was at least 10-fold higher than MRP1 mRNA expression. MRP2 immunostaining was observed in 87% (33/38) of HCC samples. MRP2 was localized in the plasma membrane in a polarized fashion, either in trabecular structures resembling the canalicular membrane or in the luminal membrane when cells had a pseudoglandular arrangement. MRP3 was detected in all samples examined (9/9) by RT-PCR and by immunofluorescence microscopy. MRP3 was localized to the basolateral membrane of carcinoma cells. Double-label immunofluorescence microscopy with antibodies specific for MRP2 or MRP3 indicated that carcinoma cells expressed both MRP isoforms simultaneously. When MRP1 was detected by immunofluorescence microscopy, it was localized on the intracellular membranes of carcinoma cells. Thus, plasma membrane expression of MRP2 and MRP3, but not of MRP1, can contribute to the MDR phenotype of HCC.
A T Nies; J König; M Pfannschmidt; E Klar; W J Hofmann; D Keppler
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  94     ISSN:  0020-7136     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-12-17     Completed Date:  2002-01-07     Revised Date:  2007-07-24    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  492-9     Citation Subset:  IM    
Copyright Information:
Copyright 2001 Wiley-Liss, Inc.
Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
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MeSH Terms
Adenosine Triphosphate / metabolism
Carcinoma, Hepatocellular / metabolism*
Cell Membrane / metabolism
Drug Resistance, Multiple*
Drug Resistance, Neoplasm*
Fibrosis / metabolism
Liver / metabolism
Liver Neoplasms / metabolism*
Membrane Transport Proteins*
Microscopy, Fluorescence
Multidrug Resistance-Associated Proteins / biosynthesis*
Protein Isoforms
Protein Structure, Tertiary
RNA, Messenger / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Reg. No./Substance:
0/Membrane Transport Proteins; 0/Multidrug Resistance-Associated Proteins; 0/Protein Isoforms; 0/RNA, Messenger; 0/multidrug resistance-associated protein 1; 0/multidrug resistance-associated protein 2; 0/multidrug resistance-associated protein 3; 56-65-5/Adenosine Triphosphate

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