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首页> 外文期刊>Oncogene >Regulation of Bcl-2 expression by C/EBP in t(14;18) lymphoma cells.
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Regulation of Bcl-2 expression by C/EBP in t(14;18) lymphoma cells.

机译：C/EBP 对 t（14;18）淋巴瘤细胞。

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摘要

In follicular lymphomas with the t(14;18) translocation, there is increased expression of the bcl-2 gene, which is dependent upon regulatory elements within the bcl-2 5' flanking region and the immunoglobulin heavy-chain gene enhancers. We found that t(14;18) lymphomas expressed C/EBPalpha, which is not normally expressed in B lymphocytes. Expression of C/EBPalpha increased bcl-2 expression, and two regions of the bcl-2 P2 promoter that mediated this effect were identified. C/EBPbeta was also able to increase bcl-2 promoter activity through these sites. The 5' site was GC-rich and did not contain a C/EBP consensus sequence; however, C/EBP was observed to interact with this site both in vitro by EMSA and in vivo by chromatin immunoprecipitation assay. The 3' region contained the Cdx site, which mediates the effect of A-Myb on the bcl-2 promoter. In vivo binding studies revealed that C/EBP interacted with this region of the bcl-2 promoter as well. Decreased expression of C/EBP factors due to targeting oftheir transcripts by siRNA molecules resulted in downregulation of Bcl-2 protein. We conclude that C/EBPalpha and C/EBPbeta contribute to the deregulated expression of Bcl-2 in t(14;18) lymphoma cells.
机译：在滤泡性淋巴瘤中，t（14;18） 易位时，BCL-2 基因的表达增加，这依赖于 BCL-2 5' 侧翼区域内的调控元件和免疫球蛋白重链基因增强子。我们发现 t（14;18） 淋巴瘤表达 C/EBPα，通常不表达在 B 淋巴细胞中。C/EBPα 的表达增加了 bcl-2 的表达，并鉴定了介导这种作用的 bcl-2 P2 启动子的两个区域。C/EBPbeta 还能够通过这些位点增加 bcl-2 启动子活性。5' 位点富含 GC，不包含 C/EBP 共识序列;然而，通过EMSA观察到C/EBP在体外和通过染色质免疫沉淀测定在体内与该位点相互作用。3' 区域包含 Cdx 位点，该位点介导 A-Myb 对 bcl-2 启动子的作用。体内结合研究表明，C/EBP 也与 bcl-2 启动子的该区域相互作用。由于 siRNA 分子靶向 C/EBP 因子的转录本，导致 C/EBP 因子的表达降低导致 Bcl-2 蛋白下调。我们得出结论，C/EBPalpha 和 C/EBPbeta 有助于 t（14;18）淋巴瘤细胞。

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