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首页> 外文期刊>Molecular cancer research: MCR >Bcl-2 Overexpression Leads to Increases in Suppressor of Cytokine Signaling-3 Expression in B Cells and De novo Follicular Lymphoma.
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Bcl-2 Overexpression Leads to Increases in Suppressor of Cytokine Signaling-3 Expression in B Cells and De novo Follicular Lymphoma.

机译:Bcl-2过表达导致B细胞和新生滤泡性淋巴瘤中细胞因子信号传导3表达的抑制因子增加。

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The t(14;18)(q32;q21), resulting in deregulated expression of B-cell-leukemia/lymphoma-2 (Bcl-2), represents the genetic hallmark in human follicular lymphomas. Substantial evidence supports the hypothesis that the t(14;18) and Bcl-2 overexpression are necessary but not solely responsible for neoplastic transformation and require cooperating genetic derangements for neoplastic transformation to occur. To investigate genes that cooperate with Bcl-2 to influence cellular signaling pathways important for neoplastic transformation, we used oligonucleotide microarrays to determine differential gene expression patterns in CD19+ B cells isolated from Emu-Bcl-2 transgenic mice and wild-type littermate control mice. Fifty-seven genes were induced and 94 genes were repressed by >/=2-fold in Emu-Bcl-2 transgenic mice (P < 0.05). The suppressor of cytokine signaling-3 (SOCS3) gene was found to be overexpressed 5-fold in B cells from Emu-Bcl-2 transgenic mice. Overexpression of Bcl-2 in both mouse embryo fibroblast-1 and hematopoietic cell lines resulted in induction of SOCS3 protein, suggesting a Bcl-2-associated mechanism underlying SOCS3 induction. Immunohistochemistry with SOCS3 antisera on tissue from a cohort of patients with de novo follicular lymphoma revealed marked overexpression of SOCS3 protein that, within the follicular center cell region, was limited to neoplastic follicular lymphoma cells and colocalized with Bcl-2 expression in 9 of 12 de novo follicular lymphoma cases examined. In contrast, SOCS3 protein expression was not detected in the follicular center cell region of benign hyperplastic tonsil tissue. These data suggest that Bcl-2 overexpression leads to the induction of activated signal transducer and activator of transcription 3 (STAT3) and to the induction of SOCS3, which may contribute to the pathogenesis of follicular lymphoma.
机译:t(14; 18)(q32; q21)导致B细胞白血病/淋巴瘤2(Bcl-2)的表达失调,代表了人类滤泡性淋巴瘤的遗传特征。大量证据支持以下假设:t(14; 18)和Bcl-2过表达是必要的,但并非仅负责赘生性转化,并且要求发生赘生性转化的合作基因错位。为了研究与Bcl-2合作影响对肿瘤转化重要的细胞信号通路的基因,我们使用了寡核苷酸微阵列来确定从Emu-Bcl-2转基因小鼠和野生型同窝仔小鼠分离的CD19 + B细胞中的差异基因表达模式。在Emu-Bcl-2转基因小鼠中,诱导了57个基因并且94个基因被抑制了> / = 2倍(P <0.05)。发现在Emu-Bcl-2转基因小鼠的B细胞中,细胞因子信号转导3(SOCS3)基因的抑制子过表达5倍。 Bcl-2在小鼠胚胎成纤维细胞1和造血细胞系中的过表达导致SOCS3蛋白的诱导,表明SOCS3诱导的Bcl-2相关机制。在一群新生滤泡性淋巴瘤患者的组织中用SOCS3抗血清进行的免疫组织化学分析显示,在滤泡中心细胞区域内,SOCS3蛋白的过度表达明显局限于赘生性滤泡性淋巴瘤细胞,并且在12分之9中与Bcl-2表达共定位新生滤泡性淋巴瘤病例进行了检查。相反,在良性增生扁桃体组织的滤泡中心细胞区域未检测到SOCS3蛋白表达。这些数据表明,Bcl-2过表达导致激活信号转导子和转录激活子3(STAT3)的诱导以及SOCS3的诱导,这可能与滤泡性淋巴瘤的发病机理有关。

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