Association of nuclear membrane protein lamin B1 with necrosis and apoptosis in cell death induced by 5-fluoro-2′-deoxyuridine
Association of nuclear membrane protein lamin B1 with necrosis and apoptosis in cell death induced by 5-fluoro-2′-deoxyuridine
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DOI：
10.1080/15257770802086864
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发表时间：
2008-01-01
影响因子：
1.3
通讯作者：
Kim, Hye-Sook
中科院分区：
文献类型：
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作者：
Sato, Akira;Hiramoto, Akiko;Kim, Hye-Sook
我们报告抗癌5-氟-2 '-脱氧尿苷（FUdR）对小鼠癌细胞系FM 3A的细胞毒性，使用子代克隆F28-7及其变体F28-7-A。F28-7-A和F28-7-7-A细胞在此过程中的细胞死亡形态不同，F28-7细胞为坏死，而F28-7-A细胞为凋亡。在这些细胞暴露于FUdR前的蛋白质组学分析中，核内膜蛋白核纤层蛋白B1在F28-7中上调，但在F28-7-A中未上调，这表明核纤层蛋白B1可能具有调节细胞死亡形态的功能。通过使用小干扰RNA技术进行F28-7细胞中核纤层蛋白B1表达的敲低，导致核纤层蛋白B1表达水平降低至F28-7-A中的水平。值得注意的是，这种敲低的F28-7的FUdR诱导的死亡形态是凋亡，与FUdR处理的原始F28-7中发生的坏死明显不同。因此，不再观察到坏死的肿胀特征，相反，在几乎所有检查的细胞中发生典型的细胞凋亡的细胞收缩。这一发现表明核纤层蛋白B1作为细胞死亡调节因子的新作用。
We report that anticancer 5-fluoro-2'-deoxyuridine (FUdR) shows cytotoxicity against mouse cancer cell line FM3A, using a progeny clone F28-7 and its variant F28-7-A. In this process, the cell-death morphology is different between F28-7 and F28-7-A cells, that is, necrosis in F28-7 but apoptosis in F28-7-A cells. In the proteomic analysis of these cells before their exposure to FUdR, the nuclear inner-membrane protein lamin B1 is up-regulated in F28-7 but not in F28-7-A, suggesting that lamin B1 may possess a function to regulate the morphology of cell-death. A knockdown of lamin B1 expression in F28-7 cells was performed by use of the small interfering RNA technique, resulting in a decrease of the lamin B1-expression level down to the level in F28-7-A. Remarkably, the FUdR-induced death morphology of this knocked-down F28-7 was apoptosis, definitely different from the necrosis that occurs in the FUdR-treated original F28-7. Thus, the swelling feature for the necrosis was no longer observable, and instead cell shrinkage typical of apoptosis took place in almost all the cells examined. This finding suggests a new role for lamin B1 as a regulator in cell death.