INTRINSIC DRUG-RESISTANCE IN HUMAN-KIDNEY CANCER IS ASSOCIATED WITH EXPRESSION OF A HUMAN MULTIDRUG-RESISTANCE GENE
INTRINSIC DRUG-RESISTANCE IN HUMAN-KIDNEY CANCER IS ASSOCIATED WITH EXPRESSION OF A HUMAN MULTIDRUG-RESISTANCE GENE
复制标题
DOI：
10.1200/jco.1987.5.12.1922
复制
发表时间：
1987-12-01
影响因子：
45.3
通讯作者：
GOTTESMAN, MM
中科院分区：
文献类型：
--
作者：
FOJO, AT;SHEN, DW;GOTTESMAN, MM
mdr 1基因的cDNA克隆，其表达与培养细胞的多药耐药性的发展有关，使得有可能探索人类肿瘤的多药耐药机制。我们已经发现，正常人肾脏，八个肾腺癌，和四个细胞系来源于肾腺癌表达高水平的mdr 1 mRNA。两个标准表明，人肾腺癌的原发性多药耐药至少部分是由于mdr 1基因的表达：（1）在4个具有多药耐药表型的人肾腺癌细胞系中，mdr 1 mRNA水平升高;和（2）这些肾癌细胞系中的多药耐药性被维拉帕米和奎尼丁逆转，已知在体外逆转选择用于多药耐药性的细胞系中的MDR 1相关耐药性的试剂。这些结果表明，逆转多药耐药性的适当药物干预可能使肾腺癌对阿霉素（Adria Laboratories，哥伦布，OH）和长春花生物碱等药物化疗更敏感。
The cloning of the cDNA for the mdr1 gene, whose expression is associated with the development of multidrug-resistance in cultured cells, has made it possible to explore the mechanism of multidrug resistance in human tumors. We have found that normal human kidney, six of eight adenocarcinomas of the kidney, and four cell lines derived from kidney adenocarcinomas express high levels of mdr1 mRNA. Two criteria suggest that primary multidrug resistance in human adenocarcinomas of the kidney results, at least in part, from expression of the mdr1 gene: (1) mdr1 mRNA levels are elevated in four unselected kidney adenocarcinoma cell lines that show a multidrug-resistant phenotype; and (2) multidrug resistance in these kidney cancer cell lines is reversed by verapamil and quinidine, agents known to reverse mdr1-associated drug resistance in cell lines selected for multidrug resistance in vitro. These results suggest that appropriate pharmacological intervention to reverse multidrug resistance might make adenocarcinomas of the kidney more sensitive to chemotherapy with agents such as Adriamycin (Adria Laboratories, Columbus, OH) and the vinca alkaloids.