BCL6相关转录共抑制因子MTA3由生发中心B细胞和假定生发中心来源的淋巴瘤选择性表达。
The BCL6-associated transcriptional co-repressor, MTA3, is selectively expressed by germinal centre B cells and lymphomas of putative germinal centre derivation.
作者信息
Jaye D L, Iqbal J, Fujita N, Geigerman C M, Li S, Karanam S, Fu K, Weisenburger D D, Chan W C, Moreno C S, Wade P A
机构信息
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
出版信息
J Pathol. 2007 Sep;213(1):106-15. doi: 10.1002/path.2199.
Metastasis-associated protein 3 (MTA3) is a recently described cell-type specific component of the Mi-2-NURD transcriptional co-repressor complex that is expressed in breast epithelia and germinal centre B cells. In model B cell lines, MTA3 physically interacts with BCL6 and appears to be instrumental in maintenance of the germinal centre B cell transcriptional programme that precludes premature plasmacytic differentiation. Here, we report selective, in situ cell-type specific expression of MTA3 among lymphoid cells largely confined to the germinal centre B cell compartment. Centroblasts display greater expression than smaller, less proliferative centrocytes, with undetectable expression in quiescent plasma cells. Among B cell neoplasms, germinal centre B cell-like lymphomas likewise exhibit selective expression that generally escalates with increasing proliferative capacity. MTA3 protein expression was, in accord, highly predictive of the germinal centre B cell-like gene expression profile for diffuse large B cell lymphomas. Lastly, relative repression of a subset of known BCL6 targets, including BLIMP1 and p27kip1, was highest in diffuse large B cell lymphomas that co-expressed both MTA3 and BCL6 protein. Together, these novel data suggest a role for MTA3 in BCL6-mediated lymphomagenesis in germinal centre B cell-like neoplasms.
转移相关蛋白3(MTA3)是最近被描述的Mi-2-NURD转录共抑制复合物的细胞类型特异性成分,在乳腺上皮细胞和生发中心B细胞中表达。在模型B细胞系中,MTA3与BCL6发生物理相互作用,似乎有助于维持生发中心B细胞转录程序,从而防止过早的浆细胞分化。在此,我们报道了MTA3在淋巴细胞中的选择性原位细胞类型特异性表达,主要局限于生发中心B细胞区室。中心母细胞的表达高于较小、增殖性较低的中心细胞,而在静止的浆细胞中未检测到表达。在B细胞肿瘤中,生发中心B细胞样淋巴瘤同样表现出选择性表达,通常随着增殖能力的增加而升高。同样,MTA3蛋白表达高度预测弥漫性大B细胞淋巴瘤的生发中心B细胞样基因表达谱。最后,在同时表达MTA3和BCL6蛋白的弥漫性大B细胞淋巴瘤中,包括BLIMP1和p27kip1在内的已知BCL6靶点的一个子集的相对抑制作用最高。总之,这些新数据表明MTA3在生发中心B细胞样肿瘤中BCL6介导的淋巴瘤发生中起作用。