C/EBPβ regulates transcription factors critical for proliferation and survival of multiple myeloma cells

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Item Type:	Article
Title:	C/EBPβ regulates transcription factors critical for proliferation and survival of multiple myeloma cells
Creators Name:	Pal, R., Janz, M., Galson, D.L., Gries, M., Li, S., Johrens, K., Anagnostopoulos, I., Doerken, B., Mapara, M.Y., Borghesi, L., Kardava, L., Roodman, G.D., Milcarek, C. and Lentzsch, S.
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.
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
Source:	Blood
ISSN:	0006-4971
Publisher:	American Society of Hematology
Volume:	114
Number:	18
Page Range:	3890-3898
Date:	29 October 2009
Official Publication:	https://doi.org/10.1182/blood-2009-01-201111
PubMed:	View item in PubMed

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