A multidrug resistance transporter from human MCF-7 breast cancer cells
A multidrug resistance transporter from human MCF-7 breast cancer cells
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DOI：
10.1073/pnas.95.26.15665
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发表时间：
1998-12-22
影响因子：
11.1
通讯作者：
Ross, DD
中科院分区：
文献类型：
--
作者：
Doyle, LA;Yang, WD;Ross, DD
MCF-7/AdrVp是一种多药耐药人乳腺癌亚系，在缺乏已知的多药耐药转运体（如P糖蛋白或多药耐药蛋白）过表达的情况下，其细胞内蒽环类抗癌药物积累的atp依赖性减少。RNA指纹鉴定结果显示，相对于亲代MCF-7细胞，MCF-7/AdrVp细胞中有2.4 kb mRNA过表达。mRNA编码atp结合盒转运蛋白超家族的663-aa成员，我们称之为乳腺癌抵抗蛋白（BCRP）。MCF-7乳腺癌细胞中全长BCRP cDNA的强制表达赋予对米托蒽醌、阿霉素和柔红霉素的抗性，减少柔红霉素的积累和保留，并导致克隆转染细胞中罗丹明123的atp依赖性外排增强。BCRP是一种外源转运蛋白，似乎在MCF-7/AdrVp人乳腺癌细胞的多药耐药表型中发挥重要作用。
MCF-7/AdrVp is a multidrug-resistant human breast cancer subline that displays an ATP-dependent reduction in the intracellular accumulation of anthracycline anticancer drugs in the absence of overexpression of known multidrug resistance transporters such as P glycoprotein or the multidrug resistance protein. RNA fingerprinting led to the identification of a 2.4-kb mRNA that is overexpressed in MCF-7/AdrVp cells relative to parental MCF-7 cells. The mRNA encodes a 663-aa member of the ATP-binding cassette superfamily of transporters that we term breast cancer resistance protein (BCRP). Enforced expression of the full-length BCRP cDNA in MCF-7 breast cancer cells confers resistance to mitoxantrone, doxorubicin, and daunorubicin, reduces daunorubicin accumulation and retention, and causes an ATP-dependent enhancement of the efflux of rhodamine 123 in the cloned transfected cells. BCRP is a xenobiotic transporter that appears to play a major role in the multidrug resistance phenotype of MCF-7/AdrVp human breast cancer cells.