論文 - 詳細
| RRC ID | 65422 |
|---|---|
| 著者 | Tahara K, Takizawa M, Yamane A, Osaki Y, Ishizaki T, Mitsui T, Yokohama A, Saitoh T, Tsukamoto N, Matsumoto M, Murakami H, Nojima Y, Handa H. |
| タイトル | Overexpression of B-cell lymphoma 6 alters gene expression profile in a myeloma cell line and is associated with decreased DNA damage response. |
| ジャーナル | Cancer Sci |
| Abstract |
B-cell lymphoma 6 (BCL6) attenuates DNA damage response (DDR) through gene repression and facilitates tolerance to genomic instability during immunoglobulin affinity maturation in germinal center (GC) B cells. Although BCL6 expression is repressed through normal differentiation of GC B cells into plasma cells, a recent study showed the ectopic expression of BCL6 in primary multiple myeloma (MM) cells. However, the functional roles of BCL6 in MM cells are largely unknown. Here, we report that overexpression of BCL6 in a MM cell line, KMS12PE, induced transcriptional repression of ataxia telangiectasia mutated (ATM), a DDR signaling kinase, which was associated with a reduction in γH2AX formation after DNA damage. In contrast, transcription of known targets of BCL6 in GC B cells was not affected, suggesting a cell type-specific function of BCL6. To further investigate the effects of BCL6 overexpression on the MM cell line, we undertook mRNA sequence analysis and found an upregulation in the genomic mutator activation-induced cytidine deaminase (AID) with alteration in the gene expression profile, which is suggestive of de-differentiation from plasma cells. Moreover, interleukin-6 exposure to KMS12PE led to upregulation of BCL6 and AID, downregulation of ATM, and attenuation of DDR, which were consistent with the effects of BCL6 overexpression in this MM cell line. Taken together, these results indicated that overexpression of BCL6 alters gene expression profile and confers decreased DDR in MM cells. This phenotypic change could be reproduced by interleukin-6 stimulation, suggesting an important role of external stimuli in inducing genomic instability, which is a hallmark of MM cells. |
| 巻・号 | 108(8) |
| ページ | 1556-1564 |
| 公開日 | 2017-8-1 |
| DOI | 10.1111/cas.13283 |
| PMID | 28544233 |
| PMC | PMC5543477 |
| MeSH | Ataxia Telangiectasia Mutated Proteins / genetics Cell Line, Tumor Cytidine Deaminase / genetics DNA Damage* Gene Expression Profiling / methods* Gene Expression Regulation, Neoplastic Gene Regulatory Networks Genomic Instability Humans Multiple Myeloma / genetics* Phenotype Proto-Oncogene Proteins c-bcl-6 / genetics* Sequence Analysis, RNA / methods* Up-Regulation* |
| IF | 4.966 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | CTB-1(RCB1316) |