P-glycoprotein down-regulates expression of breast cancer resistance protein in a drug-free state
P-glycoprotein down-regulates expression of breast cancer resistance protein in a drug-free state
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DOI：
10.1016/j.febslet.2008.06.036
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发表时间：
2008-07-23
期刊：
影响因子：
3.5
通讯作者：
Choi, Cheol-Hee
中科院分区：
文献类型：
--
作者：
Bark, Hyun;Xu, Hai-Dong;Choi, Cheol-Hee
本研究探讨了p -糖蛋白（Pgp）和乳腺癌抵抗蛋白（BCRP）在表达方面是否存在联系。RT- PCR和Western blot分析显示，肺癌细胞株SK- MES- 1/ WT表达BCRP。在无药状态下，BCRP表达显著。在多柔比星耐药的SK- MES- 1/ DX1000细胞中，Pgp的表达不能下调。药物抑制剂（PSC833或维拉帕米）或Pgp siRNA抑制BCRP的下调，共聚焦显微镜证实了这一点。PSC833诱导c- Jun NH2-末端激酶（JNK）和c- Jun的磷酸化，而JNK抑制剂SP600125则抑制这一作用。显性阴性c- Jun使BCRP表达降低，Pgp表达升高。这些结果表明Pgp在无药状态下下调BCRP表达，JNK/ c- Jun参与其中。(c) 2008年欧洲生化学会联合会。Elsevier b.v.版权所有。
This study investigated whether P-glycoprotein ( Pgp) and breast cancer resistance protein ( BCRP) are linked in terms of expression. RT- PCR and Western blot analyses showed that the lung cancer cell line SK- MES- 1/ WT expressed BCRP. In a drug- free state, BCRP expression was signi. cantly down- regulated in doxorubicin- resistant SK- MES- 1/ DX1000 cells overexpressing Pgp. Pharmacological inhibitors ( PSC833 or verapamil) or siRNA for Pgp inhibited the down- regulation of BCRP, which was con. rmed by confocal microscopy. PSC833 induced the phosphorylation of c- Jun NH2- terminal kinase ( JNK) and c- Jun, while the JNK inhibitor SP600125 inhibited this e. ect. Dominant negative c- Jun decreased the expression of BCRP, but increased that of Pgp. These results indicate that Pgp down- regulates BCRP expression in a drug- free state in which JNK/ c- Jun is involved. (c) 2008 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.