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C/EBP{beta} regulates transcription factors critical for proliferation and survival of multiple myeloma cells

Official URL:https://doi.org/10.1182/blood-2009-01-201111
PubMed:View item in PubMed
Creators Name:Pal, R. and Janz, M. and Galson, D.L. and Gries, M. and Li, S. and Johrens, K. and Anagnostopoulos, I. and Doerken, B. and Mapara, M.Y. and Borghesi, L. and Kardava, L. and Roodman, G.D. and Milcarek, C. and Lentzsch, S.
Journal Title:Blood
Journal Abbreviation:Blood
Page Range:3890-3898
Date:29 October 2009
Keywords:B-Lymphocytes, CCAAT-Enhancer-Binding Protein-beta, Tumor Cell Line, Cell Proliferation, Cell Survival, DNA-Binding Proteins, Down-Regulation, Neoplastic Gene Expression Regulation, Gene Silencing, Interferon Regulatory Factors, Multiple Myeloma, Genetic Promoter Regions, Proto-Oncogene Proteins c-bcl-2, Repressor Proteins, Transcription Factors, Animals, Mice
Abstract:C/EBP{beta}, also known as NF-IL6, is a transcription factor, which plays an important role in the regulation of growth and differentiation of myeloid and lymphoid cells. Mice deficient in C/EBP{beta} show impaired generation of B lymphocytes. We show that C/EBP{beta} regulates transcription factors critical for proliferation and survival in multiple myeloma. Multiple myeloma cell lines and primary multiple myeloma cells strongly expressed C/EBP{beta}, whereas normal B cells and plasma cells had little or no detectable levels of C/EBP{beta}. Silencing of C/EBP{beta} led to down-regulation of transcription factors such as IRF4, XBP1 and BLIMP1 accompanied by a strong inhibition of proliferation. Further, silencing of C/EBP{beta} led to a complete down-regulation of anti-apoptotic BCL2 expression. In ChIP assays, C/EBP{beta} directly bound to the promoter region of IRF4, BLIMP1 and BCL2. Our data indicate that C/EBP{beta} is involved in the regulatory network of transcription factors which are critical for plasma cell differentiation and survival. Targeting C/EBP{beta} may provide a novel therapeutic strategy in the treatment of multiple myeloma.
Publisher:American Society of Hematology (U.S.A.)
Item Type:Article

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