Bader P, Schilling F, Schlaud M, Girgert R, Handgretinger R, Klingebiel T, Treuner J, Liu C, Niethammer D, Beck J F
Children's Hospital, Department of Hematology and Oncology, D-72076 Tubingen, Germany.
Oncol Rep. 1999 Sep-Oct;6(5):1143-6. doi: 10.3892/or.6.5.1143.
In a series of 40 neuroblastomas we analyzed the relative mRNA levels of the MDR associated genes encoding MDR1/P-glycoprotein (MDR1), multidrug resistance associated protein (MRP), lung cancer resistance related protein (LRP) and topoisomerase IIalpha (TOPO IIalpha) by cDNA-PCR. Cyclin A (CYCA) was included to examine cellular proliferation activity. MYCN gene expression was analyzed as it was recently shown to be associated with enhanced MRP gene expression in neuroblastomas. We found that tumors with MYCN gene amplification exhibit significantly increased MYCN and MRP gene expression levels. Tumors with an allelic loss of the chromosomal 1p region showed significant (P<0.05) lower MDR1 gene expression (MDR1: 50+/-29, n=4) than tumors without (MDR1: 117+/-81, P<0.05, n=36). Moreover, significant positive correlations were found for MYCN/TOPO IIalpha (P<0.0001), MYCN/CYCA (P<0.05), TOPO IIalpha/CYCA (P<0.01), MRP/CYCA (P<0.0001) and MRP/LRP (P<0.05). Our results give evidence that MDR in neuroblastomas might be caused by multiple resistance factors and that a higher proliferation rate of neuroblastoma cells possibly based on altered MYCN gene expression is associated with enhanced MRP, CYCA and TOPO IIalpha gene expression.
在一组40例神经母细胞瘤中，我们通过cDNA - PCR分析了编码多药耐药相关蛋白MDR1/P - 糖蛋白（MDR1）、多药耐药相关蛋白（MRP）、肺癌耐药相关蛋白（LRP）和拓扑异构酶IIα（TOPO IIα）的多药耐药相关基因的相对mRNA水平。纳入细胞周期蛋白A（CYCA）以检测细胞增殖活性。分析了MYCN基因表达，因为最近研究表明其与神经母细胞瘤中MRP基因表达增强有关。我们发现，MYCN基因扩增的肿瘤显示MYCN和MRP基因表达水平显著增加。染色体1p区域等位基因缺失的肿瘤，其MDR1基因表达（MDR1：50±29，n = 4）显著低于（P<0.05）无1p区域等位基因缺失的肿瘤（MDR1：117±81，P<0.05，n = 36）。此外，还发现MYCN/TOPO IIα（P<0.0001）、MYCN/CYCA（P<0.05）、TOPO IIα/CYCA（P<0.01）、MRP/CYCA（P<0.0001）和MRP/LRP（P<0.05）之间存在显著正相关。我们的结果表明，神经母细胞瘤中的多药耐药可能由多种耐药因素引起，并且神经母细胞瘤细胞较高的增殖率可能基于MYCN基因表达改变，与MRP、CYCA和TOPO IIα基因表达增强有关。
