Korean J Pediatr Hematol Oncol.  2002 Apr;9(1):91-100.

Expression of Multidrug Resistance (MDR1) and Multidrug Resistance Associated Protein (MRP) Genes in Pediatric Malignant Solid Tumors

• Seo YK
• Jung HL
• Kim DH
• Yoo KH
• Shim JY
• Sung KW
• Koo HH
• Shin HY
• Ahn HS
• Wang KC
• Cho BK

Abstract

PURPOSE: Multidrug resistance (MDR) is one of the main obstacles in the successful anticancer chemotherapy. Classic MDR phenotype is characterized by overexpression of membrane bound permeability-glycoprotein (Pgp) drug-efflux pump, encoded by MDR1 gene. The non-Pgp MDR phenotype is caused by overexpression of multidrug resistance associated protein (MRP), another membrane transport protein, encoded by MRP gene. We examined the mRNA expression of MDR1 and MRP genes in various types of pediatric malignant solid tumors at diagnosis.
METHODS
Five fresh frozen tissue and 15 primarily cultured cell samples from 20 children diagnosed as malignant solid tumors (8 neuroblastomas, 5 medulloblastomas, 3 Burkitt lymphomas, 2 Wilms tumors, 1 each of rhabdomyosarcoma and rhabdoid tumor) were analyzed by reverse transcription-polymerase chain reaction (RT-PCR).
RESULTS
Among 20 pediatric solid tumors, MDR1 mRNA expression was observed in 14 cases (70%), and MRP mRNA expression was observed in 15 cases (75%). The co-expression of MDR1 and MRP was recognized in 12 (60%) of 20 cases. Event (death or relapse) occurred in 7 cases during observation period of median 9 months after diagnosis, and 6 of these 7 cases (86%) showed the co-expression of MDR1 and MRP.
CONCLUSION
These data suggest that MRP, like MDR1, may have an important negative impact on the outcome of chemotherapy in pediatric malignant solid tumors, and it is possible that these two genes may collaborate in causing the appearance of MDR under certain circumstances.

Keyword

Multidrug resistance; MDR1; MRP; Pediatric malignant solid tumor

MeSH Terms

Burkitt Lymphoma
Cells, Cultured
Child
Diagnosis
Drug Resistance, Multiple*
Drug Therapy
Humans
Medulloblastoma
Membranes
Multidrug Resistance-Associated Proteins*
Neuroblastoma
Phenotype
Rhabdomyosarcoma
RNA, Messenger
Wilms Tumor
Multidrug Resistance-Associated Proteins
RNA, Messenger