Li Lei, He Dalin, He Hui, Wang Xinyang, Zhang Linlin, Luo Yong, Nan Xunyi
Institute of Urology, No. 1 Hospital, Xi'an Jiaotong University, Shaanxi 710061, China.
Cancer Lett. 2006 May 18;236(2):259-68. doi: 10.1016/j.canlet.2005.05.034. Epub 2005 Oct 10.
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 h 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.
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细胞凋亡至关重要。PML在细胞死亡调节中发挥作用的机制尚不清楚。我们之前的研究表明，PML的过表达通过诱导细胞凋亡和细胞周期停滞来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诱导稳定细胞系。我们发现，PML表达的增加显著抑制了UM-UC-2/PML克隆细胞的生长，并在诱导后24小时出现明显的大量细胞凋亡，而UM-UC-2/PMEP4细胞则没有。我们还研究了PML对UM-UC-2细胞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。此外，膀胱癌UM-UC-2细胞中PML表达的增加降低了Survivin的表达，并上调了Caspase-3和裂解的PARP的表达，这些表明PML可能通过Caspase依赖途径调节细胞凋亡。我们的结果证明了一种新的PML诱导细胞凋亡的机制，即通过下调Survivin和激活Caspase依赖途径来实现。
