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

Rekha Pal, Martin Janz, Deborah L. Galson, Margarete Gries, Shirong Li, Korinna Jöhrens, Ioannis Anagnostopoulos, Bernd Dörken, Markus Y. Mapara, Lisa Borghesi, Lela Kardava, G. David Roodman, Christine Milcarek, Suzanne Lentzsch

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

CCAAT/enhancer-binding protein β (C/EBPβ), 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/EBPβ show impaired generation of B lymphocytes. We show that C/EBPβ regulates transcription factors critical for proliferation and survival in multiple myeloma. Multiple myeloma cell lines and primary multiple myeloma cells strongly expressed C/EBPβ, whereas normal B cells and plasma cells had little or no detectable levels of C/EBPβ. Silencing of C/EBPβ led to down-regulation of transcription factors such as IRF4, XBP1, and BLIMP1 accompanied by a strong inhibition of proliferation. Further, silencing of C/EBPβ led to a complete downregulation of antiapoptotic B-cell lymphoma 2 (BCL2) expression. In chromatin immunoprecipitation assays, C/EBPβ directly bound to the promoter region of IRF4, BLIMP1, and BCL2. Our data indicate that C/EBPβ is involved in the regulatory network of transcription factors that are critical for plasma cell differentiation and survival. Targeting C/EBPβ may provide a novel therapeutic strategy in the treatment of multiple myeloma.

Original languageEnglish (US)
Pages (from-to)3890-3898
Number of pages9
JournalBlood
Volume114
Issue number18
DOIs
StatePublished - Oct 29 2009

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint Dive into the research topics of 'C/EBPβ regulates transcription factors critical for proliferation and survival of multiple myeloma cells'. Together they form a unique fingerprint.

  • Cite this

    Pal, R., Janz, M., Galson, D. L., Gries, M., Li, S., Jöhrens, K., Anagnostopoulos, I., Dörken, B., Mapara, M. Y., Borghesi, L., Kardava, L., David Roodman, G., Milcarek, C., & Lentzsch, S. (2009). C/EBPβ regulates transcription factors critical for proliferation and survival of multiple myeloma cells. Blood, 114(18), 3890-3898. https://doi.org/10.1182/blood-2009-01-201111