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多药耐药基因1/ P糖蛋白和多药耐药相关蛋白在儿童实体瘤中的表达

Expression of MDR1/p-glycoprotein and multidrug resistance-associated protein in childhood solid tumours.

作者信息

Oda Y, Röse I, Radig K, Wagemann W, Mittler U, Roessner A

机构信息

Department of Pathology, Otto-von-Guericke University Magdeburg, Germany.

出版信息

Virchows Arch. 1997 Feb;430(2):99-105. doi: 10.1007/BF01008030.

Abstract

We evaluated the expression of MDR1/p-glycoprotein in paediatric tumours using reverse transcriptase polymerase chain reaction (RT-PCR), RNA dot blot analysis, and immunohistochemistry on formalin fixed paraffin-embedded material with JSB-1 and C-219 monoclonal antibodies, and compared these three techniques. The expression of multidrug resistance-associated protein (MRP) gene was examined by RT-PCR assay. We studied MDR1/p-glycoprotein and MRP expression in 13 samples from 10 neuroblastoma patients, 11 samples from 10 nephroblastoma patients, 2 rhabdomyosarcomas, 1 adrenocortical carcinoma and 10 benign tumours or tumour-like lesions. Eleven of 13 neuroblastomas, 7 of 11 nephroblastomas, 2 rhabdomyosarcomas, 1 adrenocortical carcinoma, and 7 of 10 benign tumours or tumour-like lesions showed MDR1 PCR products. By RNA dot blot analysis, MDR1 transcripts were detectable in 11 of 34 specimens. Immunohistochemically, we detected positive reaction products for JSB-1 in 26 of 36 samples. There was a significant correlation between the immunoreactivity for JSB-1 and the expression of MDR1 mRNA expression by RT-PCR (P = 0.0001). However, the presence of p-glycoprotein immunostaining does not correlate with the MDR1 expression shown by RT-PCR in every case. As for MRP mRNA expression, 9 of 13 neuroblastomas and 10 of 11 nephroblastomas revealed PCR products.

摘要

我们运用逆转录聚合酶链反应(RT-PCR)、RNA斑点印迹分析以及免疫组织化学方法,使用JSB-1和C-219单克隆抗体,对福尔马林固定石蜡包埋材料上的小儿肿瘤中MDR1/p-糖蛋白的表达进行了评估,并比较了这三种技术。通过RT-PCR检测多药耐药相关蛋白(MRP)基因的表达。我们研究了10例神经母细胞瘤患者的13个样本、10例肾母细胞瘤患者的11个样本、2例横纹肌肉瘤、1例肾上腺皮质癌以及10例良性肿瘤或肿瘤样病变中MDR1/p-糖蛋白和MRP的表达情况。13例神经母细胞瘤中的11例、11例肾母细胞瘤中的7例、2例横纹肌肉瘤、1例肾上腺皮质癌以及10例良性肿瘤或肿瘤样病变中的7例显示出MDR1 PCR产物。通过RNA斑点印迹分析,在34个标本中的11个检测到了MDR1转录本。免疫组织化学检测显示,在36个样本中的26个检测到了JSB-1的阳性反应产物。JSB-1的免疫反应性与RT-PCR检测的MDR1 mRNA表达之间存在显著相关性(P = 0.0001)。然而,在每种情况下,p-糖蛋白免疫染色的存在与RT-PCR显示的MDR1表达并不相关。至于MRP mRNA表达,13例神经母细胞瘤中的9例和11例肾母细胞瘤中的10例显示出PCR产物。

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