Overexpression of PML induced apoptosis in bladder cancer cell by Caspase dependent pathway
Overexpression of PML induced apoptosis in bladder cancer cell by Caspase dependent pathway
复制标题
DOI：
10.1016/j.canlet.2005.05.034
复制
发表时间：
2006-05-18
期刊：
影响因子：
9.7
通讯作者：
Nan, Xunyi
中科院分区：
文献类型：
--
作者：
Li, Lei;He, Dalin;Nan, Xunyi
早幼粒细胞白血病基因（PML）编码一种生长/肿瘤抑制蛋白，该蛋白对于响应各种凋亡信号诱导凋亡是必需的。PML在调节细胞死亡中发挥作用的机制仍不清楚。我们前期的研究表明PML过表达可通过诱导细胞凋亡和细胞周期阻滞抑制膀胱癌细胞的生长。为了进一步阐明PML诱导膀胱癌细胞凋亡的机制，我们构建了一个PML诱导的稳定细胞系。我们发现PML的高表达显著抑制了UM-UC-2/PML克隆细胞的生长，并在诱导后的24小时内出现明显的大量凋亡，而UM-UC-2/PMEP 4细胞则没有。我们还研究了PML对UM-UC-2细胞周期分布的影响。我们发现PML的过表达导致细胞周期停滞在G1期。另外，PML在膀胱癌UM-UC-2细胞中表达增加，Survivin表达降低，Caspase-3表达上调，PARP表达增加，提示PML可能通过Caspase依赖性途径调控细胞凋亡。我们的研究结果表明PML通过下调Survivin和激活Caspase依赖性途径诱导细胞凋亡的新机制。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
The promyelocytic leukemia gene (PML) encodes a growth/tumor suppressor protein that is essential for the induction of apoptosis in response to various apoptotic signals. The mechanism by which PML plays a role in the regulation of cell death is still unknown. Our previous study demonstrated that overexpression of PML suppress the growth of bladder cancer cells by inducing apoptosis and cell cycle arrest. To further elucidate the mechanism of PML induced apoptosis in bladder cancer, we constructed a PML inducible stable cell line. We found that the increased expression of PML significantly inhibit the growth of the UM-UC-2/PML clone cells and present apparent massive apoptosis in 24 It post-induction, while the UM-UC-2/PMEP4 cells are not. We also examined the effect of PML on the cell cycle distribution in UM-UC-2 cells. We showed overexpression of PML cause a cell cycle arrest in G1 phase. In additional, increased expression of PML in bladder cancer UM-UC-2 cells reduce Survivin expression and up regulated Caspase-3, and cleaved PARP expression, these suggested that PML might regulate apoptosis through Caspase dependent pathways. Our results demonstrate a novel mechanism of PML-induced apoptosis by down-regulation of Survivin and activation of Caspase dependent pathway. (c) 2005 Elsevier Ireland Ltd. All rights reserved.