IL-6-induced Bcl6 variant 2 supports IL-6-dependent myeloma cell proliferation and survival through STAT3 |
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Authors: | Tsuyama Naohiro Danjoh Inaho Otsuyama Ken-Ichiro Obata Masanori Tahara Hidetoshi Ohta Tsutomu Ishikawa Hideaki |
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Institution: | Department of Bio-Signal Analysis, Yamaguchi University Graduate School of Medicine, Minami Kogushi 1-1-1, Ube, Yamaguchi 755-8505, Japan. tsuyama@yamaguchi-u.ac.jp |
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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. |
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Keywords: | Myeloma IL-6 Microarray Bcl6 STAT3 p53 PDCD4 Trichostatin A |
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