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

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, we...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2005-11, Vol.337 (1), p.201-208
Main Authors: Tsuyama, Naohiro, Danjoh, Inaho, Otsuyama, Ken-ichiro, Obata, Masanori, Tahara, Hidetoshi, Ohta, Tsutomu, Ishikawa, Hideaki
Format: Article
Language:English
Subjects:
5' Flanking Region
60 APPLIED LIFE SCIENCES
Bcl6
Cell Line, Tumor
CELL PROLIFERATION
Cell Proliferation - drug effects
Cell Survival - drug effects
DNA
DNA-Binding Proteins - biosynthesis
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
GROWTH
Humans
IL-6
Interleukin-6 - pharmacology
LYMPHOMAS
Microarray
Multiple Myeloma - genetics
Multiple Myeloma - metabolism
Multiple Myeloma - pathology
Myeloma
ONCOGENES
p53
PDCD4
PLASMA CELLS
Proto-Oncogene Proteins c-bcl-6
Receptors, Estrogen - metabolism
RNA
SENSITIVITY
STAT3
STAT3 Transcription Factor
Trans-Activators - metabolism
Trichostatin A
Up-Regulation
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Summary: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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2005.09.036