Silencing of the microtubule-associated proteins doublecortin-like and doublecortin-like kinase-long induces apoptosis in neuroblastoma cells

被引：31
|
作者：
Verissimo, Carla S. [1 ]
Molenaar, Jan J.
Meerman, John [2 ,3 ]
Puigvert, Jordi Carreras [2 ,3 ]
Lamers, Fieke
Koster, Jan
Danen, Erik H. J. [2 ,3 ]
van de Water, Bob [2 ,3 ]
Versteeg, Rogier
Fitzsimons, Carlos P. [1 ]
Vreugdenhil, Erno [1 ]
机构：
[1] Gorlaeus Labs, Leiden Amsterdam Ctr Drug Res, Div Med Pharmacol, NL-2300 RA Leiden, Netherlands
[2] Univ Amsterdam, Acad Med Ctr, Dept Human Genet, NL-1105 AZ Amsterdam, Netherlands
[3] Leiden Univ, Div Toxicol, Leiden Amsterdam Ctr Drug Res, Leiden, Netherlands
来源：
ENDOCRINE-RELATED CANCER | 2010年 / 17卷 / 02期
关键词：
GENE-EXPRESSION; NEURONAL MIGRATION; MOLECULAR-BIOLOGY; MITOTIC SPINDLES; PROGENITOR CELLS; SPLICE VARIANTS; DCX SUPERFAMILY; RADIAL GLIA; MITOCHONDRIA; ACTIVATION;
D O I：
10.1677/ERC-09-0301
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Doublecortin-like kinase-long (DCLK-long) and doublecortin-like (DCL) are two splice variants of DCLK gene. DCL and DCLK-long are microtubule-associated proteins with specific expression in proliferative neural progenitor cells. We have tested the hypothesis that knockdown of DCL/DCLK-long by RNA interference technology will induce cell death in neuroblastoma (NB) cells. First, we analyzed the expression of DCL and DCLK-long in several human neuroblastic tumors, other tumors, and normal tissues, revealing high expression of both DCL and DCLK-long in NB and glioma. Secondly, gene expression profiling revealed numerous differentially expressed genes indicating apoptosis induction after DCL/DCLK-long knockdown in NB cells. Finally, apoptosis was confirmed by time-lapse imaging of phosphatidylserine translocation, caspase-3 activation, live/dead double staining assays, and fluorescence-activated cell sorting. Together, our results suggest that silencing DCL/DCLK-long induces apoptosis in NB cells. Endocrine-Related Cancer (2010) 17 399-414
引用
收藏
页码：399 / 414
页数：16
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