IL-6-induced Bcl6 variant 2 supports IL-6-dependent myeloma cell proliferation and survival through STAT3
- Department of Bio-Signal Analysis, Yamaguchi University Graduate School of Medicine, Minami Kogushi 1-1-1, Ube, Yamaguchi 755-8505 (Japan)
- Genetics Division, Center of Medical Genomics, National Cancer Center Research Institute, Tsukiji, Chuo-ku, Tokyo (Japan)
- Department of Cellular and Molecular Biology, Hiroshima University Graduate School of Medicine, Kasumi 1-2-3, Minami ward, Hiroshima 732-0001 (Japan)
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.
- OSTI ID:
- 20713434
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 337, Issue 1; Other Information: DOI: 10.1016/j.bbrc.2005.09.036; PII: S0006-291X(05)02051-6; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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