EXPRESSION OF THE MULTIDRUG RESISTANCE, MDR1, GENE IN NEUROBLASTOMAS

被引:112
|
作者
GOLDSTEIN, LJ
FOJO, AT
UEDA, K
CRIST, W
GREEN, A
BRODEUR, G
PASTAN, I
GOTTESMAN, MM
机构
[1] NCI, MOLEC BIOL LAB, 9000 ROCKVILLE PIKE, 37-2E18, BETHESDA, MD 20205 USA
[2] ST JUDE CHILDRENS RES HOSP, DEPT HEMATOL ONCOL, MEMPHIS, TN 38101 USA
[3] UNIV TENNESSEE, CTR HLTH SCI,COLL MED,DEPT PEDIAT, DIV HEMATOL ONCOL, MEMPHIS, TN 38163 USA
[4] WASHINGTON UNIV, SCH MED, DEPT PEDIAT, ST LOUIS, MO 63110 USA
关键词
D O I
10.1200/JCO.1990.8.1.128
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Metastatic neuroblastoma is a childhood malignancy that is frequently responsive to chemotherapy with doxorubicin, vincristine, and teniposide (VM26), among other drugs, but in the majority of treated patients, the tumor recurs during or after chemotherapy. In this work, we have examined the hypothesis that the development of resistance to chemotherapy in neuroblastoma might be related to the expression of the human MDR1 gene, which encodes a multidrug transporter that functions as an energy-dependent drug efflux pump. RNA samples from 49 neuroblastomas were analyzed, including 31 from untreated and 18 from treated patients. MDR1 RNA was detectable in the majority of treated and untreated tumors using a sensitive, semiquantitative slot blot assay. Of the samples from treated patients, five of 18 were found to have high MDR1 RNA levels, whereas only three of 31 from untreated patients had high MDR1 levels, a statistically significant difference (P < .01). These results show that high levels of MDR1 RNA are often associated with resistance to chemotherapy in neuroblastoma and suggest that they may contribute to this resistance. Many of the neuroblastoma samples were also evaluated for N-myc amplification but there was no correlation between N-myc copy number and the level of MDR1 mRNA expression.
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收藏
页码:128 / 136
页数:9
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