Laboratory of Cellular Signal Analysis, Department of Bio-Signal Analysis, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-Kogushi, Ube 755-8505, Japan.
Int J Hematol. 2010 Mar;91(2):267-75. doi: 10.1007/s12185-009-0474-3. Epub 2010 Jan 5.
CD56 is frequently detected on primary myeloma cells from more than 80% patients with overt myeloma. In order to clarify the possible mechanisms of CD56 expression in human myeloma, we underwent screening for potential targets by microarray analysis, where the CD56(+) myeloma cell lines showed markedly increased expressions of transcription factors involved in the neuronal cell lineage compared to the CD56(-) myeloma cell lines. Here, we show that among the SOX family of transcription factors, SOX4 was highly up-regulated and SOX1 was down-regulated in the CD56(+) myeloma cell lines as well as in primary myeloma cases as confirmed by the RT-PCR. ChIP analysis of the CD56 promoter region showed specific bindings of SOX4 in the CD56(+) and SOX1 in the CD56(-) myeloma cell lines, respectively. shRNA against SOX1 failed to induce CD56 expression in CD56(-) myeloma cell line, U266. On the contrary, over-expression of SOX4 in the CD56(-) myeloma cell line could induce the CD56 expression. Silencing of SOX4 by shRNA transfection down-regulated CD56 expression and induced apoptosis to CD56(+) human myeloma cell line, AMO1. Thus, induction of SOX4 gene expression might be responsible for the CD56 expression in human myeloma cells.
CD56 在超过 80%的显性骨髓瘤患者的原发性骨髓瘤细胞中经常被检测到。为了阐明人类骨髓瘤中 CD56 表达的可能机制，我们通过微阵列分析进行了潜在靶点的筛选，结果显示 CD56(+)骨髓瘤细胞系与 CD56(-)骨髓瘤细胞系相比，涉及神经元细胞谱系的转录因子表达明显增加。在这里，我们表明在 SOX 转录因子家族中，SOX4 在 CD56(+)骨髓瘤细胞系以及原发性骨髓瘤病例中高度上调，而 SOX1 下调，这通过 RT-PCR 得到了证实。CD56 启动子区域的 ChIP 分析显示，SOX4 在 CD56(+)骨髓瘤细胞系中特异性结合，而 SOX1 在 CD56(-)骨髓瘤细胞系中特异性结合。针对 SOX1 的 shRNA 未能诱导 CD56(-)骨髓瘤细胞系 U266 中的 CD56 表达。相反，SOX4 在 CD56(-)骨髓瘤细胞系中的过表达可以诱导 CD56 表达。shRNA 转染沉默 SOX4 下调 CD56 表达并诱导 CD56(+)人骨髓瘤细胞系 AMO1 凋亡。因此，SOX4 基因表达的诱导可能是人类骨髓瘤细胞中 CD56 表达的原因。
