FUNCTIONAL-ROLE FOR THE 170-KDA TO 180-KDA GLYCOPROTEIN SPECIFIC TO DRUG-RESISTANT TUMOR-CELLS AS REVEALED BY MONOCLONAL-ANTIBODIES

FUNCTIONAL-ROLE FOR THE 170-KDA TO 180-KDA GLYCOPROTEIN SPECIFIC TO DRUG-RESISTANT TUMOR-CELLS AS REVEALED BY MONOCLONAL-ANTIBODIES
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DOI:
10.1073/pnas.83.20.7785
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发表时间:
1986-10-01
影响因子:
11.1
通讯作者:
TSURUO, T
TSURUO, T
中科院分区:
综合性期刊1区
文献类型:
--
作者:
HAMADA, H;TSURUO, T

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相对分子大小为170-180 kDa的质膜糖蛋白的过表达在不同的多药耐药人和动物细胞系中一直存在,尽管该蛋白在多药耐药中的功能作用尚不清楚。本文报道了两株抗人髓性白血病耐阿霉素细胞株(K-562/ADM)的单克隆抗体。这些抗体,命名为MRK 16和MRK 17,对K-562/ADM和耐阿霉素的人卵巢癌细胞系(2780 AD)具有特异性反应性。MRK 16调节耐药细胞中长春新碱和放线菌素D的转运,而MRK 17特异性抑制耐药细胞的生长。两种抗体均识别170至180 kDa的糖蛋白。这些数据表明,170- 180-kDa的糖蛋白直接或间接地参与药物转运机制和多药耐药肿瘤细胞系的增殖。
An overexpression of the plasma membrane glycoprotein of relative molecular size 170-180 kDa is consistently found in different multidrug-resistant human and animal cell lines, although the functional role of the protein in multidrug resistance is not known. Two monoclonal antibodies that interfere with biochemical functions were generated against the human myelogenous leukemia K-562 cells resistant to adriamycin (K-562/ADM). These antibodies, designated MRK16 and MRK17, are specifically reactive to K-562/ADM and a human ovarian cancer cell line resistant to adriamycin (2780AD). MRK16 modulated vincristine and actinomycin D transport in the resistant cells, while MRK17 specificially inhibited the growth of the resistant cells. Both antibodies recognized the 170- to 180-kDa glycoprotein. These data indicate that the 170- to 180-kDa glycoprotein is involved, directly or indirectly, in the drug transport mechanisms and the proliferation of multidrug-resistant tumor cell lines.