STAT6 and STAT1 are essential antagonistic regulators of cell survival in classical Hodgkin lymphoma cell line
STAT6 and STAT1 are essential antagonistic regulators of cell survival in classical Hodgkin lymphoma cell line
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DOI：
10.1038/leu.2009.103
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发表时间：
2009-10-01
期刊：
影响因子：
11.4
通讯作者：
Pfitzner, E.
中科院分区：
文献类型：
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作者：
Baus, D.;Nonnenmacher, F.;Pfitzner, E.
经典霍奇金淋巴瘤（cHL）是一种以信号通路异常激活为特征的恶性淋巴系统疾病。在cHL细胞Hodgkin和Reed/斯滕贝格细胞中观察到了（Ja）在bar下（K）在bar下酶/（S）在bar信号（T）在bar转换器下和（A）在bar激活子（T）在bar转录下（JAK/STAT）通路中的几个组分的组成性激活。在这项研究中，我们研究了STAT 6在cHL细胞系中的功能，并表明STAT 6促进这些细胞的存活。对表达STAT 6-shRNA（短发夹RNA）的cHL细胞系进行微阵列表达分析以分析STAT 6介导的存活机制。一些已鉴定的具有潜在重要调节功能的基因也在拉莫斯B细胞中受到白细胞介素（IL）-4依赖性调节，并且可以确认STAT 6与几个基因的调节区的结合，这表明这些是直接的STAT 6靶基因。重要的是，STAT 6敲低增加了STAT 1的表达和激活以及已知STAT 1靶基因的表达，表明这些信号分子之间存在交叉调节。STAT 1的强制表达能够诱导cHL细胞系L1236的凋亡。这些发现表明STAT 6和STAT 1均可作为cHL发病机制中重要的拮抗调节因子。Leukemia（2009）23，1885-1893; doi：10.1038/leu.2009.103; 2009年5月14日在线发表
Classical Hodgkin lymphoma (cHL) is a malignant lymphoid disorder characterized by aberrant activation of signaling pathways. Constitutive activation of several components of the (Ja) under bar nus (K) under bar inase/(S) under bar ignal (T) under bar ransducer and (A) under bar ctivator of (T) under bar ranscription (JAK/STAT) pathway has been observed in Hodgkin and Reed/Sternberg cells, the tumor cells of cHL. In this study, we investigate the function of STAT6 in cHL cell lines and show that STAT6 promotes survival of these cells. Microarray expression analysis of STAT6-shRNA (short hairpin RNA)expressing cHL cell lines was carried out to analyze the STAT6-mediated survival mechanism. Some of the identified genes with potentially important regulatory functions were also interleukin (IL)-4 dependently regulated in Ramos B cells and binding of STAT6 to the regulatory regions of several genes could be confirmed, indicating that these are direct STAT6 target genes. Importantly, STAT6 knockdown increased the expression and activation of STAT1 as well as the expression of known STAT1 target genes, indicating a cross-regulation between these signaling molecules. Forced expression of STAT1 was able to induce apoptosis in cHL cell line L1236. These findings indicate that both STAT6 and STAT1 can act as important antagonistic regulators in the pathogenesis of cHL. Leukemia (2009) 23, 1885-1893; doi: 10.1038/leu.2009.103; published online 14 May 2009