IL-6-induced Bcl6 variant 2 supports IL-6-dependent myeloma cell proliferation and survival through STAT3.
IL-6-induced Bcl6 variant 2 supports IL-6-dependent myeloma cell proliferation and survival through STAT3.
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DOI：
10.1016/j.bbrc.2005.09.036
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发表时间：
2005-11
影响因子：
3.1
通讯作者：
N. Tsuyama;I. Danjoh;K. Otsuyama;Masanori Obata;H. Tahara;T. Ohta;H. Ishikawa
中科院分区：
文献类型：
--
作者：
N. Tsuyama;I. Danjoh;K. Otsuyama;Masanori Obata;H. Tahara;T. Ohta;H. Ishikawa
IL-6是骨髓瘤细胞的生长和存活因子，尽管其通过基因表达诱导骨髓瘤细胞增殖的机制在很大程度上尚不清楚。微阵列分析显示，在正常浆细胞中不存在的一些b细胞淋巴瘤相关癌基因，如Bcl6，在IL-6依赖性骨髓瘤细胞系中被IL-6上调。我们发现Bcl6变体2被STAT3上调。ChIP和EMSA实验显示STAT3结合在变异2 DNA的上游区域。Bcl6的直接靶基因p53的表达在il -6刺激的细胞中下调，这一过程被HDAC抑制剂破坏。Bcl6通过引入小发夹RNA被敲除，导致增殖减少和对DNA损伤剂的敏感性增加。因此，stat3诱导的Bcl6变体2似乎产生了一个重要的IL-6信号，支持IL-6依赖性骨髓瘤细胞的增殖和存活。
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.