Interferon γ is a strong, STAT1-dependent direct inducer of BCL6 expression in multiple myeloma cells

Dorina Ujvari, Noemi Nagy, Harsha S. Madapura, Tomasz Kallas, Marijke C.L. Kröhnke, Leif Stenke, Eva Klein, D. Salamon

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

B-cell CLL/lymphoma 6 (BCL6) is a transcriptional master regulator that can repress more than 1200 potential target genes. It exerts oncogenic effects through the inhibition of differentiation, DNA damage sensing and apoptosis in several human hematopoietic malignancies, including multiple myeloma (MM). The multifunctional cytokine interferon γ (IFNγ) exerts pro-apoptotic and anti-proliferative effects on MM cells in vitro, at least partially through the inhibition of the effects of interleukin 6 (IL6), one of the most important growth factor of MM and a strong inducer of BCL6 expression. However, IFNγ was also reported to directly upregulate BCL6 in several cell types. These observations prompted us to analyze the effect of IFNγ on BCL6 expression in MM cells. We discovered that among several myeloma growth/survival factors tested (including IL6, oncostatin M, insulin-like growth factor 1, tumor necrosis factor α and IFNα) IFNγ was the strongest inducer of BCL6 mRNA and protein expression in MM cell lines. IFNγ induced upregulation of BCL6 was dependent on the classical STAT1 signaling pathway, and affected both major BCL6 variants. Interestingly, although IFNα induced stronger STAT1 phosphorylation than IFNγ it only slightly upregulated BCL6 in MM lines. We proved that IFNα induced BCL6 upregulation was limited by the concomitant activation of STAT5 signaling. We assume that BCL6 upregulation may represent a potentially pro-tumorigenic effect of IFNγ signaling in MM cells.

Original languageEnglish
Pages (from-to)502-508
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume498
Issue number3
DOIs
Publication statusPublished - Apr 6 2018

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Keywords

  • BCL6
  • IFNγ
  • Multiple myeloma
  • STAT1
  • STAT5

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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