TY - JOUR
T1 - Silencing of the microtubule-associated proteins doublecortin-like and doublecortin-like kinase-long induces apoptosis in neuroblastoma cells
AU - Verissimo, Carla S.
AU - Molenaar, Jan J.
AU - Meerman, John
AU - Puigvert, Jordi Carreras
AU - Lamers, Fieke
AU - Koster, Jan
AU - Danen, Erik H.J.
AU - Van De Water, Bob
AU - Versteeg, Rogier
AU - Fitzsimons, Carlos P.
AU - Vreugdenhil, Erno
PY - 2010/6
Y1 - 2010/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77953600210&partnerID=8YFLogxK
U2 - 10.1677/ERC-09-0301
DO - 10.1677/ERC-09-0301
M3 - Article
C2 - 20228126
AN - SCOPUS:77953600210
SN - 1351-0088
VL - 17
SP - 399
EP - 414
JO - Endocrine-Related Cancer
JF - Endocrine-Related Cancer
IS - 2
ER -