DECREASED CCAAT/ENHANCER BINDING PROTEIN β EXPRESSION INHIBITS THE GROWTH OF GLIOBLASTOMA CELLS

被引:32
作者
Aguilar-Morante, D. [1 ,2 ]
Cortes-Canteli, M. [1 ,2 ]
Sanz-Sancristobal, M. [1 ,2 ]
Santos, A. [3 ]
Perez-Castillo, A. [1 ,2 ]
机构
[1] Univ Autonoma Madrid, CSIC, Inst Invest Biomed, Madrid 28029, Spain
[2] Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid 28029, Spain
[3] Univ Complutense Madrid, Fac Med, Dept Bioquim & Biol Mol, Madrid, Spain
关键词
C/EBP beta; glioblastoma; invasion; proliferation; shRNA; EXPERIMENTAL BRAIN-TUMORS; C/EBP-BETA; IN-VIVO; SKIN TUMORIGENESIS; MAMMARY-GLAND; DIFFERENTIATION; GLIOMA; PROLIFERATION; SURVIVAL; INJURY;
D O I
10.1016/j.neuroscience.2010.12.025
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
C/EBP beta is a leucine-zipper transcription factor implicated in the control of metabolism, development, cell differentiation, and proliferation. However, it remains unclear its role in tumor development. Here, we show that down-regulation of C/EBP beta by RNA interference inhibits proliferation in the GL261 murine glioblastoma cell line, induces an arrest of the cell cycle at the G0/G1 boundary, and diminishes their transformation capacity and migration. In addition, we show that C/EBP beta regulates the expression of several DNA damage response- and invasion-related genes. Lastly, C/EBP beta depletion significantly retards tumor onset and prolongs survival in a murine orthotopic brain tumor model. Immunohistochemical analysis revealed a significant diminution of proliferating cell nuclear antigen (PCNA) labeling in tumors derived from C/EBP beta-depleted GL261 cells compared with that in controls. These results show, for the first time, the dependence of glioma cells on C/EBP beta and suggest a potential role of this transcription factor in glioma development. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:110 / 119
页数:10
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