MULTIDRUG RESISTANCE GENE (MDR1) EXPRESSION IN HUMAN BRAIN-TUMORS
MULTIDRUG RESISTANCE GENE (MDR1) EXPRESSION IN HUMAN BRAIN-TUMORS
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DOI：
10.3171/jns.1991.75.6.0941
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发表时间：
1991-12-01
影响因子：
4.1
通讯作者：
COLVIN, OM
中科院分区：
文献类型：
--
作者：
NABORS, MW;GRIFFIN, CA;COLVIN, OM
中枢神经系统（CNS）以外的许多类型的癌症的多药耐药性已被发现是由于多药耐药基因MDR 1的过表达，其基因产物P-糖蛋白作为许多抗癌药物的膜结合外排泵。 为了检测脑肿瘤是否过度表达MDR 1基因，对25例脑肿瘤标本进行了北方印迹分析：10例胶质瘤，8例脑膜瘤，3例神经鞘瘤，1例恶性淋巴瘤和3例脑转移瘤。 本文还分析了10例新鲜冷冻的正常脑各部位尸检标本。 印迹与P-32标记的中国仓鼠互补脱氧核糖核酸（cDNA）和P-32标记的人MDR 1 cDNA杂交。 使用中国仓鼠探针在两个肿瘤（一个蝶骨翼脑膜瘤和一个转移性前列腺肿瘤）中检测到MDR 1基因信使核糖核酸（mRNA），使用人类探针在一个CNS淋巴瘤中检测到MDR 1基因信使核糖核酸（mRNA）。 正常脑组织新鲜冰冻尸检标本不能提取完整的mRNA。 用鼠单克隆抗体C219免疫组化染色检查了17个肿瘤的P-糖蛋白：8个胶质瘤，8个脑膜瘤和1个颅咽管瘤。 2例胶质瘤和3例脑膜瘤的瘤细胞及6例胶质瘤和2例脑膜瘤内的血管P-糖蛋白染色阳性。 10例正常脑组织标本中有7例血管P糖蛋白染色阳性，但无脑实质细胞染色。 这项研究表明，MDR 1基因可以在正常脑，恶性，良性和转移性病变检测。 P-糖蛋白可以存在于肿瘤血管中，即使在肿瘤细胞中看不到。 虽然P-糖蛋白在肿瘤血管中的作用需要进一步研究和更清楚地定义，但恶性原发性脑肿瘤的耐药性可能不仅来自肿瘤细胞，而且来自肿瘤血管系统。
Multidrug resistance for many types of cancer outside the central nervous system (CNS) has been found to be due to the overexpression of the multidrug resistance gene MDR1, of which the gene-product P-glycoprotein acts as a membrane-bound efflux pump for many anticancer drugs. To examine whether brain tumors overexpress the MDR1 gene, 25 brain-tumor specimens were subjected to Northern blot analysis: 10 gliomas, eight meningiomas, three schwannomas, one malignant lymphoma, and three tumors metastatic to the brain. Ten fresh-frozen autopsy specimens of various parts of normal brain were also analyzed. Blots were hybridized with P-32-labeled Chinese hamster complementary deoxyribonucleic acid (cDNA) and P-32-labeled human MDR1 cDNA. The MDR1 gene messenger ribonucleic acid (mRNA) was detected in two tumors using the Chinese hamster probe (one sphenoid wing meningioma and one metastatic prostate tumor) and in one CNS lymphoma using the human probe. Intact mRNA could not be extracted from the fresh-frozen autopsy specimens of normal brain. Seventeen tumors were examined for P-glycoprotein by immunohistochemical staining using murine monoclonal antibody C219: eight gliomas, eight meningiomas, and one craniopharyngioma. The neoplastic cells from two gliomas and three meningiomas and the blood vessels within six gliomas and two meningiomas stained positively for P-glycoprotein. Seven of 10 normal brain specimens stained positively for P-glycoprotein in blood vessels but no specimen demonstrated staining of parenchymal cells. This study demonstrates that the MDR1 gene can be detected in normal brain, and in malignant, benign, and metastatic lesions. P-glycoprotein can be present in tumor blood vessels even when it is not seen in neoplastic cells. Although the role of P-glycoprotein in tumor blood vessels needs to be further examined and more clearly defined, drug resistance in malignant primary brain tumors may result from characteristics not solely of neoplastic cells but also tumor vasculature.