Expression of Multidrug Resistance (MDR1) and Multidrug Resistance Associated Protein (MRP) Genes in Pediatric Malignant Solid Tumors.
- Author:
Yu Kyung SEO
1
;
Hye Lim JUNG
;
Dong Hyun KIM
;
Keon Hee YOO
;
Jung Yeon SHIM
;
Ki Woong SUNG
;
Hong Hoe KOO
;
Hee Young SHIN
;
Hyo Seop AHN
;
Kyu Chang WANG
;
Byung Kyu CHO
Author Information
1. Department of Pediatrics, Sungkyunkwan University School of Medicine, Korea. jungped@samsung.co.kr
- Publication Type:Original Article
- Keywords:
Multidrug resistance;
MDR1;
MRP;
Pediatric malignant solid tumor
- MeSH:
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
- From:Korean Journal of Pediatric Hematology-Oncology
2002;9(1):91-100
- CountryRepublic of Korea
- Language:Korean
-
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.
