Feng Yan-Bin, Lin De-Chen, Shi Zhi-Zhou, Wang Xiao-Chun, Shen Xiao-Ming, Zhang Yu, Du Xiao-Li, Luo Man-Li, Xu Xin, Han Ya-Ling, Cai Yan, Zhang Zi-Qiang, Zhan Qi-Min, Wang Ming-Rong
State Key Laboratory of Molecular Oncology, Cancer Institute Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Int J Cancer. 2009 Feb 1;124(3):578-88. doi: 10.1002/ijc.23990.
PLK1 is essential for the maintenance of genomic stability during mitosis. In our study, we found that overexpression of PLK1 was an independent prognostic factor (RR=4.253, p=0.020) and significantly correlated with survivin, an antiapoptotic protein, in esophageal squamous cell carcinoma (ESCC). Reverse transcription-polymerase chain reaction and fluorescence in situ hybridization (FISH) revealed upregulation of PLK1 mRNA and amplification of PLK1 gene, respectively. Depletion of PLK1 activated the intrinsic apoptotic pathway, which was substantiated by loss of mitochondrial membrane potential, reduction of Mcl-1 and Bcl-2 as well as activation of caspase-9. Coimmunoprecipitation and confocal microscopy displayed that PLK1 was associated with survivin and PLK1 depletion led to downregulation of survivin. Cotransfection of survivin constructs could partially reverse PLK1-depletion-induced apoptosis. These data suggest that PLK1 might be a useful prognostic marker and a potential therapeutic target for ESCC. Survivin is probably involved in antiapoptotic function of PLK1.
PLK1对于有丝分裂期间基因组稳定性的维持至关重要。在我们的研究中，我们发现PLK1的过表达是食管鳞状细胞癌（ESCC）中的一个独立预后因素（RR = 4.253，p = 0.020），并且与抗凋亡蛋白survivin显著相关。逆转录-聚合酶链反应和荧光原位杂交（FISH）分别揭示了PLK1 mRNA的上调和PLK1基因的扩增。PLK1的缺失激活了内源性凋亡途径，这通过线粒体膜电位的丧失、Mcl-1和Bcl-2的减少以及caspase-9的激活得到证实。免疫共沉淀和共聚焦显微镜显示PLK1与survivin相关，并且PLK1的缺失导致survivin的下调。survivin构建体的共转染可以部分逆转PLK1缺失诱导的凋亡。这些数据表明PLK1可能是ESCC的一个有用的预后标志物和潜在的治疗靶点。Survivin可能参与了PLK1的抗凋亡功能。
