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

作者：Aguilar Morante D; Cortes Canteli M; Sanz Sancristobal M; Santos A; Perez Castillo A^*

来源：Neuroscience, 2011, 176: 110-119.

DOI：10.1016/j.neuroscience.2010.12.025

• C/EBP beta
• glioblastoma
• invasion
• proliferation
• shRNA

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.

• 出版日期2011-3-10