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KMID : 0387820020090010091
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Clinical Pediatric Hematology-Oncology
2002 Volume.9 No. 1 p.91 ~ p.100
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Expression of Multidrug Resistance (MDR1) and Multidrug Resistance Associated Protein (MRP) Genes in Pediatric Malignant Solid Tumors
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Seo Yu-Kyungd
Jung Hye-Lim
Kim Dong-Hyun
Ryu Kun-Hee
Shim Jung-Yeon
Sung Ki-Woong
Koo Hong-Hoe
Shin Hee-Young
Ahn Hyo-Seop
Cho Byung-Kyu
Wang Kyu-Chang
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Abstract
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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.
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KEYWORD
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Multidrug resistance, MDR1, MRP, Pediatric malignant solid tumors
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