QUANTITATIVE-ANALYSIS OF MDR1 (MULTIDRUG RESISTANCE) GENE-EXPRESSION IN HUMAN TUMORS BY POLYMERASE CHAIN-REACTION
QUANTITATIVE-ANALYSIS OF MDR1 (MULTIDRUG RESISTANCE) GENE-EXPRESSION IN HUMAN TUMORS BY POLYMERASE CHAIN-REACTION
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DOI：
10.1073/pnas.87.18.7160
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发表时间：
1990-09-01
影响因子：
11.1
通讯作者：
RONINSON, IB
中科院分区：
文献类型：
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作者：
NOONAN, KE;BECK, C;RONINSON, IB
肿瘤细胞对化疗药物的耐药性是肿瘤化疗成功的主要障碍。在人类细胞中，编码跨膜外排泵(P-糖蛋白)的mdr1基因的表达会导致细胞内积累减少，并导致对各种亲脂性药物(多药耐药；MDR)的耐药性下降。体外筛选的细胞株中的MDR水平已被证明与MDR1mRNA和P-糖蛋白的稳态水平相关。在细胞耐药性增加几倍的细胞中，mdr1的表达水平接近常规检测的极限。多药耐药基因的表达常见于化疗后的人类肿瘤以及未经化疗药物治疗的某些但并非所有类型的临床难治性肿瘤。我们设计了一种基于聚合酶链式反应的高度敏感、特异和定量的方法来测量临床标本中mdr1基因的水平。我们用这种方法检测了mdr1基因在MDR细胞系和>；300正常组织、肿瘤衍生细胞系和未经治疗的肿瘤的临床标本中的表达，这些类型的肿瘤很少用标准的分析方法观察到mdr1的表达。聚合酶链式反应在大多数实体瘤和白血病中发现低水平的MDR1表达。在不同类型的肿瘤中，没有检测到mdr1表达的样本的频率不同；mdr1阴性的样本在已知对化疗相对敏感的肿瘤类型中最为常见。
The resistance of tumor cells to chemotherapeutic drugs is a major obstacle to successful cancer chemotherapy. In human cells, expression of the MDR1 gene, encoding a transmembrane efflux pump (P-glycoprotein), leads to decreased intracellular accumulation and resistance to a variety of lipophilic drugs (multidrug resistance; MDR). The levels of MDR in cell lines selected in vitro have been shown to correlate with the steady-state levels of MDR1 mRNA and P-glycoprotein. In cells with a severalfold increase in cellular drug resistance, MDR1 expression levels are close to the limits of detection by conventional assays. MDR1 expression has been frequently observed in human tumors after chemotherapy and in some but not all types of clinically refractory tumors untreated with chemotherapeutic drugs. We have devised a highly sensitive, specific, and quantitative protocol for measuring the levels of MDR1 mRNA in clincial samples, based on the polymerase chain reaction. We have used this assay to measure MDR1 gene expression in MDR cell lines and >300 normal tissues, tumor-derived cell lines, and clinical specimens of untreated tumors of the types in which MDR1 expression was rarely observed by standard assays. Low levels of MDR1 expresison were found by polymerase chain reaction in most solid tumors and leukemias tested. The frequency of sample without detectable MDR1 expression varied among different types of tumors; MDR1-negative samples were most common among tumor types known to be relatively responsive to chemotherapy.