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

47 Citations (Scopus)

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
Externally publishedYes

Fingerprint

CCAAT-Enhancer-Binding Proteins
Multiple Myeloma
Transcription Factors
Cells
B-Cell Lymphoma
Plasma Cells
B-Lymphocytes
Down-Regulation
CCAAT-Enhancer-Binding Protein-beta
Plasmas
Lymphocytes
Chromatin Immunoprecipitation
Myeloid Cells
Genetic Promoter Regions
Chromatin
Cell Differentiation
Assays
Cell Survival

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Pal, R., Janz, M., Galson, D. L., Gries, M., Li, S., Jöhrens, K., ... 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

C/EBPβ regulates transcription factors critical for proliferation and survival of multiple myeloma cells. / Pal, Rekha; Janz, Martin; Galson, Deborah L.; Gries, Margarete; Li, Shirong; Jöhrens, Korinna; Anagnostopoulos, Ioannis; Dörken, Bernd; Mapara, Markus Y.; Borghesi, Lisa; Kardava, Lela; Roodman, G. David; Milcarek, Christine; Lentzsch, Suzanne.

In: Blood, Vol. 114, No. 18, 29.10.2009, p. 3890-3898.

Research output: Contribution to journalArticle

Pal, R, Janz, M, Galson, DL, Gries, M, Li, S, Jöhrens, K, Anagnostopoulos, I, Dörken, B, Mapara, MY, Borghesi, L, Kardava, L, Roodman, GD, Milcarek, C & Lentzsch, S 2009, 'C/EBPβ regulates transcription factors critical for proliferation and survival of multiple myeloma cells', Blood, vol. 114, no. 18, pp. 3890-3898. https://doi.org/10.1182/blood-2009-01-201111
Pal, Rekha ; Janz, Martin ; Galson, Deborah L. ; Gries, Margarete ; Li, Shirong ; Jöhrens, Korinna ; Anagnostopoulos, Ioannis ; Dörken, Bernd ; Mapara, Markus Y. ; Borghesi, Lisa ; Kardava, Lela ; Roodman, G. David ; Milcarek, Christine ; Lentzsch, Suzanne. / C/EBPβ regulates transcription factors critical for proliferation and survival of multiple myeloma cells. In: Blood. 2009 ; Vol. 114, No. 18. pp. 3890-3898.
@article{c4359673e28f4e8b897a95fa815bf031,
title = "C/EBPβ regulates transcription factors critical for proliferation and survival of multiple myeloma cells",
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.",
author = "Rekha Pal and Martin Janz and Galson, {Deborah L.} and Margarete Gries and Shirong Li and Korinna J{\"o}hrens and Ioannis Anagnostopoulos and Bernd D{\"o}rken and Mapara, {Markus Y.} and Lisa Borghesi and Lela Kardava and Roodman, {G. David} and Christine Milcarek and Suzanne Lentzsch",
year = "2009",
month = "10",
day = "29",
doi = "10.1182/blood-2009-01-201111",
language = "English (US)",
volume = "114",
pages = "3890--3898",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "18",

}

TY - JOUR

T1 - C/EBPβ regulates transcription factors critical for proliferation and survival of multiple myeloma cells

AU - Pal, Rekha

AU - Janz, Martin

AU - Galson, Deborah L.

AU - Gries, Margarete

AU - Li, Shirong

AU - Jöhrens, Korinna

AU - Anagnostopoulos, Ioannis

AU - Dörken, Bernd

AU - Mapara, Markus Y.

AU - Borghesi, Lisa

AU - Kardava, Lela

AU - Roodman, G. David

AU - Milcarek, Christine

AU - Lentzsch, Suzanne

PY - 2009/10/29

Y1 - 2009/10/29

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=70449717285&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70449717285&partnerID=8YFLogxK

U2 - 10.1182/blood-2009-01-201111

DO - 10.1182/blood-2009-01-201111

M3 - Article

C2 - 19717648

AN - SCOPUS:70449717285

VL - 114

SP - 3890

EP - 3898

JO - Blood

JF - Blood

SN - 0006-4971

IS - 18

ER -