1. Decreased CCAAT/enhancer binding protein β expression inhibits the growth of glioblastoma cells
- Author
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Angel Santos, Ana Perez-Castillo, Marta Cortes-Canteli, Marina Sanz-SanCristobal, Diana Aguilar-Morante, Ministerio de Educación y Ciencia (España), Instituto de Salud Carlos III, and Consejo Superior de Investigaciones Científicas (España)
- Subjects
Male ,Cellular differentiation ,Blotting, Western ,Biology ,Polymerase Chain Reaction ,Mice ,Cell Movement ,Glioma ,Cell Line, Tumor ,medicine ,Animals ,Neoplasm Invasiveness ,Transcription factor ,Cell Proliferation ,Ccaat-enhancer-binding proteins ,Cell growth ,Brain Neoplasms ,General Neuroscience ,CCAAT-Enhancer-Binding Protein-beta ,Gene Expression Profiling ,Cell cycle ,medicine.disease ,Molecular biology ,Immunohistochemistry ,Proliferating cell nuclear antigen ,Mice, Inbred C57BL ,Gene Expression Regulation ,Cell culture ,biology.protein ,RNA Interference ,Glioblastoma - 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. © 2011 IBRO., This work was supported by the Ministerio de Educacion y Ciencia grant SAF2007-62811 (to A.P.-C). CIBERNED is founded by the Instituto de Salud Carlos III. D.A.-M is a fellow of the Consejo Superior de Investigaciones Científicas.
- Published
- 2011