LYMPHOID NEOPLASIA C/EBP regulates transcription factors critical for proliferation and survival of multiple myeloma cells
نویسندگان
چکیده
CCAAT/enhancer-bindingprotein (C/EBP ), also known as nuclear factor–interleukin-6 (NF-IL6), is a transcription factor that plays an important role in the regulation of growth and differentiation of myeloid and lymphoid cells. Mice deficient in C/EBP show impaired generation of B lymphocytes. We show that C/EBP regulates transcription factors critical for proliferation and survival in multiple myeloma. Multiple myeloma cell lines and primary multiple myeloma cells strongly expressed C/EBP , whereas normal B cells and plasma cells had little or no detectable levels of C/EBP . Silencing of C/EBP 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 led to a complete downregulation of antiapoptotic B-cell lymphoma 2 (BCL2) expression. In chromatin immunoprecipitation assays, C/EBP directly bound to the promoter region of IRF4, BLIMP1, and BCL2. Our data indicate that C/EBP is involved in the regulatory network of transcription factors that are critical for plasma cell differentiation and survival. Targeting C/EBP may provide a novel therapeutic strategy in the treatment of multiple myeloma. (Blood. 2009;114:3890-3898)
منابع مشابه
C/EBPbeta regulates transcription factors critical for proliferation and survival of multiple myeloma cells.
CCAAT/enhancer-binding protein beta (C/EBPbeta), also known as nuclear factor-interleukin-6 (NF-IL6), is a transcription factor that plays an important role in the regulation of growth and differentiation of myeloid and lymphoid cells. Mice deficient in C/EBPbeta show impaired generation of B lymphocytes. We show that C/EBPbeta regulates transcription factors critical for proliferation and surv...
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