Abstract
C/EBPβ 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/EBPβ 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/EBPβ regulates the expression of several DNA damage response- and invasion-related genes. Lastly, C/EBPβ 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/EBPβ-depleted GL261 cells compared with that in controls. These results show, for the first time, the dependence of glioma cells on C/EBPβ and suggest a potential role of this transcription factor in glioma development.
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