Mislocalization of membrane proteins associated with multidrug resistance in cisplatin-resistant cancer cell lines.
Mislocalization of membrane proteins associated with multidrug resistance in cisplatin-resistant cancer cell lines.
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发表时间：
2003-09
期刊：
影响因子：
11.2
通讯作者：
Xing-jie Liang;D. Shen;S. Garfield;M. Gottesman
中科院分区：
文献类型：
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作者：
Xing-jie Liang;D. Shen;S. Garfield;M. Gottesman
[(14)C]卡铂和[(3)H]甲氨蝶呤在对卡铂、甲氨蝶呤和亚砷酸钠交叉耐药的单步KB表皮样腺癌(KB-CP)细胞中的蓄积减少。在这些KB-CP细胞中，多药耐药相关蛋白(MRP)1和其他膜蛋白(如叶酸结合蛋白)的错误定位伴随着多药耐药。MRP1在单步变异体中没有减少，而是在细胞质中积累，其表观分子量发生了变化，可能是由于耐药细胞中糖基化的减少。用高尔基凝集素-GSII和内质网标记物Bip/GRP78的抗体对这个低密度隔室进行部分标记。用(35)S-蛋氨酸和(35)S-半胱氨酸脉冲追逐标记MRP1，并对细胞表面的MRP1进行脉冲追逐生物素化，结果表明膜蛋白的错误定位主要是由于质膜蛋白循环的缺陷，也表现为溶酶体的酸化缺陷。细胞毒性物质在KB-CP细胞中积累的减少可能是由于载体蛋白和/或转运蛋白未能定位到质膜所致。
The accumulation of [(14)C]carboplatin and [(3)H]methotrexate is reduced in single-step KB epidermoid adenocarcinoma (KB-CP) cells, which are cross-resistant to carboplatin, methotrexate, and sodium arsenite. In these KB-CP cells, multidrug resistance is accompanied by mislocalization of multidrug resistance associated protein (MRP) 1 and other membrane proteins such as folate-binding protein. MRP1 was not decreased in amount in single-step variants but accumulates in a cytoplasmic fraction, and its apparent molecular weight was altered probably because of reduced glycosylation in resistant cells. This low-density compartment was partially labeled with antibodies to lectin-GSII (a Golgi marker) and Bip/GRP78 (an endoplasmic reticulum marker). Pulse-chase labeling of MRP1 with (35)S-methionine and (35)S-cysteine and pulse-chase biotinylation of cell surface MRP1 suggests that membrane protein mislocalization is caused mainly by a defect of plasma membrane protein recycling, manifested also as a defect in acidification of lysosomes. The reduced accumulation of cytotoxic compounds in the KB-CP cells is presumed to result from the failure of carrier proteins and/or transporters to localize to the plasma membrane.