Ren Ke, Gou Xin, Xiao Mingzhao, He Weiyang, Kang Jian
Department of Urology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong Distrct, Chongqing, 400016, People's Republic of China.
Pathol Oncol Res. 2019 Jan;25(1):341-348. doi: 10.1007/s12253-017-0353-9. Epub 2017 Nov 9.
To find the exact downstream effector of Pim-2 pathway in prostate cancer cells, and to determine the means by which it affects prostate cancer. XIAP, Pim-2 and p-eIF4B expressions were detected in PCA and BPH tissues. Then the Pim-2 and XIAP expressions were manipulated using transfection or RNAi in prostatic cells. Finally, Pim-2/eIF4B/XIAP levels were examined in PCA tissues with different clinicopathologic features. XIAP was significantly higher in PCA than in BPH tissues. When Pim-2 was transfected into noncancerous prostate epithelial cells RWPE-1, Pim-2, p-eIF4B and XIAP were all significantly increased and the apoptosis rate was significantly decreased. When XIAP was transfected into RWPE-1 cells, XIAP was significantly increased with no impact on Pim-2, p-eIF4B and the apoptosis rate. When Pim-2 SiRNA was transfected into prostate cancer cells PC-3, Pim-2, p-eIF4B and XIAP were significantly decreased and the apoptosis rate was significantly increased. When XIAP SiRNA was transfected into PC-3 cells, XIAP was significantly decreased with no impact on Pim-2, p-eIF4B and apoptosis rate. Pim-2, p-eIF4B and XIAP were all significantly higher in PCA tissues with GS ≥8 than those with GS ≤7. XIAP is the downstream factor of Pim-2 pathway in prostate cancer cells. Pim-2 and XIAP cooperate in inhibiting the apoptosis of prostate cancer cells. The activation of Pim-2 pathway may predict higher GS in prostate cancer.
寻找前列腺癌细胞中Pim-2信号通路的确切下游效应分子，并确定其影响前列腺癌的机制。检测前列腺癌（PCA）组织和良性前列腺增生（BPH）组织中XIAP、Pim-2和磷酸化真核细胞起始因子4B（p-eIF4B）的表达。然后在前列腺细胞中通过转染或RNA干扰来调控Pim-2和XIAP的表达。最后，检测具有不同临床病理特征的PCA组织中Pim-2/eIF4B/XIAP的水平。PCA组织中XIAP的表达显著高于BPH组织。将Pim-2转染至非癌性前列腺上皮细胞RWPE-1中时，Pim-2、p-eIF4B和XIAP均显著升高，细胞凋亡率显著降低。将XIAP转染至RWPE-1细胞中时，XIAP显著升高，而对Pim-2、p-eIF4B和细胞凋亡率无影响。将Pim-2小干扰RNA（SiRNA）转染至前列腺癌细胞PC-3中时，Pim-2、p-eIF4B和XIAP显著降低，细胞凋亡率显著升高。将XIAP SiRNA转染至PC-3细胞中时，XIAP显著降低，而对Pim-2、p-eIF4B和细胞凋亡率无影响。在 Gleason评分（GS）≥8的PCA组织中，Pim-2、p-eIF4B和XIAP均显著高于GS≤7的组织。XIAP是前列腺癌细胞中Pim-2信号通路的下游因子。Pim-2和XIAP协同抑制前列腺癌细胞的凋亡。Pim-2信号通路的激活可能预示前列腺癌具有更高的GS。
