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

Autor/innen

  • R. Pal
  • M. Janz
  • D.L. Galson
  • M. Gries
  • S. Li
  • K. Johrens
  • I. Anagnostopoulos
  • B. Doerken
  • M.Y. Mapara
  • L. Borghesi
  • L. Kardava
  • G.D. Roodman
  • C. Milcarek
  • S. Lentzsch

Journal

  • Blood

Quellenangabe

  • Blood 114 (18): 3890-3898

Zusammenfassung

  • 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.


DOI

doi:10.1182/blood-2009-01-201111