Overexpression of nucleolin in chronic lymphocytic leukemia cells induces stabilization of bcl2 mRNA
Overexpression of nucleolin in chronic lymphocytic leukemia cells induces stabilization of bcl2 mRNA
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DOI：
10.1182/blood-2006-08-043257
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发表时间：
2007-04-01
期刊：
影响因子：
20.3
通讯作者：
Fernandes, Daniel J.
中科院分区：
文献类型：
--
作者：
Otake, Yoko;Soundararajan, Sridharan;Fernandes, Daniel J.
B细胞慢性淋巴细胞性白血病（CLL）的特征在于由于bcl 2癌基因过表达而对凋亡具有抗性的克隆性B细胞的积累。进行研究以确定在来自健康志愿者的CD 19（+）CLL细胞中观察到的bcl-2蛋白上调的机制，与CD 19（+）B细胞相比。CLL细胞中bcl-2蛋白水平的11倍高与核仁素（一种bcl 2 mRNA稳定蛋白）的胞浆水平的26倍升高呈正相关。bcl 2异质核/bcl 2 mRNA（hnRNA）/mRNA的比率和bcl 2 mRNA的衰减率在细胞提取物中的测量表明，3倍高的稳态水平的bcl 2 mRNA在CLL细胞中的结果增加bcl 2 mRNA的稳定性。核仁素在CLL细胞的细胞核和细胞质中均有表达，而在正常B细胞中核仁素仅在细胞核中表达。在正常B细胞提取物中加入重组人核仁素可显著减慢bcl 2 mRNA的衰减速率。siRNA敲低MCF-7细胞中核仁素导致bcl 2 mRNA和蛋白水平降低，但β-肌动蛋白无变化。提示bcl-2在CLL细胞中的过表达与核仁素稳定bcl-2 mRNA有关。
B-cell chronic lymphocytic leukemia (CLL) is characterized by the accumulation of clonal B cells that are resistant to apoptosis as a result of bcl2 oncogene overexpression. Studies were done to determine the mechanism for the up-regulation of bcl-2 protein observed in CD19(+) CLL cells compared with CD19(+) B cells from healthy volunteers. The 11-fold higher level of bcl-2 protein in CLL cells was positively correlated with a 26-fold elevation in the cytosolic level of nucleolin, a bcl2 mRNA-stabilizing protein. Measurements of the bcl2 heterogeneous nuclear/bcl2 mRNA (hnRNA)/mRNA ratios and the rates of bcl2 mRNA decay in cell extracts indicated that the 3-fold higher steady-state level of bcl2 mRNA in CLL cells was the result of increased bcl2 mRNA stability. Nucleolin was present throughout the nucleus and cytoplasm of CLL cells, whereas in normal B cells nucleolin was only detected in the nucleus. The addition of recombinant human nucleolin to extracts of normal B cells markedly slowed the rate of bcl2 mRNA decay. SiRNA knockdown of nucleolin in MCF-7 cells resulted in decreased levels of bcl2 mRNA and protein but no change in beta-actin. These results indicate that bcl-2 overexpression in CLL cells is related to stabilization of bcl2 mRNA by nucleolin.