IL-6-induced Bcl6 variant 2 supports IL-6-dependent myeloma cell proliferation and survival through STAT3

Naohiro Tsuyama, Inaho Danjoh, Ken Ichiro Otsuyama, Masanori Obata, Hidetoshi Tahara, Tsutomu Ohta, Hideaki Ishikawa

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

IL-6 is a growth and survival factor for myeloma cells, although the mechanism by which it induces myeloma cell proliferation through gene expression is largely unknown. Microarray analysis showed that some B-cell lymphoma-associated oncogenes such as Bcl6, which is absent in normal plasma cells, were upregulated by IL-6 in IL-6-dependent myeloma cell lines. We found that Bcl6 variant 2 was upregulated by STAT3. ChIP assay and EMSA showed that STAT3 bound to the upstream region of variant 2 DNA. Expression of p53, a direct target gene of Bcl6, was downregulated in the IL-6-stimulated cells, and this process was impaired by an HDAC inhibitor. Bcl6 was knocked down by introducing small hairpin RNA, resulting in decreased proliferation and increased sensitivity to a DNA damaging agent. Thus, STAT3-inducible Bcl6 variant 2 appears to generate an important IL-6 signal that supports proliferation and survival of IL-6-dependent myeloma cells.

Original languageEnglish
Pages (from-to)201-208
Number of pages8
JournalBiochemical and biophysical research communications
Volume337
Issue number1
DOIs
Publication statusPublished - 2005 Nov 11
Externally publishedYes

Keywords

  • Bcl6
  • IL-6
  • Microarray
  • Myeloma
  • PDCD4
  • STAT3
  • Trichostatin A
  • p53

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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