Expression of MRP and cMOAT in childhood neuroblastomas and malignant liver tumors and its relevance to clinical behavior

Jpn J Cancer Res. 1998 Dec;89(12):1276-83. doi: 10.1111/j.1349-7006.1998.tb00524.x.


Advanced neuroblastoma and malignant liver tumor are representative childhood cancers for which combined chemotherapy including cisplatin and doxorubicin is routinely performed. The prognosis of patients with tumors which develop multiple drug resistance (MDR) is unfavorable. To elucidate the role of multidrug resistance-associated protein (MRP) and canalicular multispecific organic anion transporter (cMOAT) in the clinical behavior of the tumors, we examined 42 neuroblastomas and 10 malignant liver tumors for the expressions of MRP and cMOAT by quantitative RNA-polymerase chain reaction (PCR). The amplification and expression of N-myc oncogene in the neuroblastomas were also investigated. We found a close association between MRP and N-myc expression in each neuroblastoma sample but no significant relationship between MRP expression and the patients' outcome. The forced expression of N-myc failed to enhance the expression of MRP in N-myc transfected neuroblastoma cell lines. cMOAT was rarely expressed in the neuroblastomas, but was frequently expressed in the malignant liver tumors. The expression of MRP and cMOAT in the childhood liver tumors was more common and higher, especially in advanced cases with a poor outcome, than that observed in normal liver or in 9 hepatocellular carcinomas from adult patients. The enhanced expression of these genes might be characteristic of childhood malignant liver tumors and related to their clinical chemoresistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / biosynthesis*
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / physiology
  • Anion Transport Proteins
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / mortality
  • Carrier Proteins / biosynthesis*
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology
  • Child
  • Disease Progression
  • Drug Resistance, Neoplasm*
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic*
  • Genes, myc
  • Humans
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / mortality
  • Multidrug Resistance-Associated Proteins
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / physiology
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology
  • Neuroblastoma / drug therapy
  • Neuroblastoma / metabolism*
  • Neuroblastoma / mortality
  • Organ Specificity
  • Polymerase Chain Reaction
  • Proto-Oncogene Proteins c-myc / biosynthesis
  • Proto-Oncogene Proteins c-myc / physiology*
  • Recombinant Fusion Proteins / physiology
  • Survival Analysis
  • Transfection
  • Treatment Outcome


  • ATP-Binding Cassette Transporters
  • Anion Transport Proteins
  • Carrier Proteins
  • Multidrug Resistance-Associated Proteins
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • Proto-Oncogene Proteins c-myc
  • Recombinant Fusion Proteins