Upregulation of stem cell genes in multidrug resistant K562 leukemia cells

被引:28
作者
Lehne, Gustav [1 ,2 ]
Grasmo-Wendler, Unn-Hilde
Berner, Jeanne-Marie
Meza-Zepeda, Leonardo A. [4 ]
Adamsen, Birgitte Lid [3 ]
Flack, Aksel [4 ]
Reiner, Andrew [4 ]
Clausen, Ole Petter Fraas [3 ]
Hovig, Eivind
Myklebost, Ola [4 ]
机构
[1] Oslo Univ Hosp, Norwegian Radium Hosp, Dept Oncol, N-0310 Oslo, Norway
[2] Oslo Univ Hosp, Rikshosp, Dept Clin Pharmacol, N-0310 Oslo, Norway
[3] Oslo Univ Hosp, Rikshosp, Dept Pathol, N-0310 Oslo, Norway
[4] Univ Oslo, Dept Mol Biosci, Norwegian Microarray Consortium, N-0316 Oslo, Norway
关键词
Stem cells; Gene amplification; Multidrug resistance; ABCB1; ABCB4; ABCB5; SEMA3D; P-GLYCOPROTEIN; DRUG-RESISTANCE; CD38; EXPRESSION; IN-VITRO; INHIBITION; APOPTOSIS; LINES; BRAIN; MDR1; GLUCOSYLCERAMIDE;
D O I
10.1016/j.leukres.2009.03.028
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The transmembrane transporter P-glycoprotein (P-gp) encoded by ABCB1, is one major cause for multidrug resistance (MDR). We compared the genomic profile and gene expression pattern of the P-gp positive K562(VCR) cells with parental P-gp negative K562(wt) cells. In K562VCR array CGH revealed amplification of ABCB1, ABCB4, ABCB5 and SEMA3D, whereas expression microarrays demonstrated upregulation of stem cell genes (e.g. KIT and HOXB4), anti-apoptotic genes (e.g. IGF1R and CCNG1), and downregulation of proapoptotic genes (e.g. CASP4, 6 and 7). Thus, K562VCR cells disclose stem cell characteristics including a range of drug resistance mechanisms possibly attained as a stem cell program switched on en bloc. (c) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1379 / 1385
页数:7
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