丝氨酸／苏氨酸激酶Pim－2在肝细胞癌组织中的表达及意义

Expression and significance of proviral integration site of murine-2 in hepatoma carcinoma

目的探讨丝氨酸／苏氨酸激酶Pim-2在肝细胞癌（HCC）中的表达及其意义。方法收集重庆医科大学附属第二医院肝胆外科2006年1月至2007年12月收治的肝细胞癌患者27例，手术切除的肝细胞癌、相应癌旁组织以及同期重庆市江津区中心医院收治的非肿瘤性肝叶切除术11例的正常肝组织为对照，并分为肝癌组织组（HCC）、癌旁组织组（PNL）和正常肝组织组（NL），分别通过实时定量聚合酶链反应（Real-timePCR）、Westernblot及凝胶迁移实验（EMSA）检测各组标本中Pim-2、核因子（NF）-κB和凋亡抑制因子5（API-5）的mRNA水平，Pim-2、tAPI－5和pAPI-5的蛋白水平及NF—KB的活性度，并对检测结果进行分析。结果Pim-2在肝细胞癌中的mRNA和蛋白水平（0．129676±O．007427、1．300000±0．232890）均较癌旁组织（0．048063±0．004113、0．970000±0．223120）和正常肝组织（0．029125±0．002911、0．470000±0．100600）中显著增高（P〈0．05）；NF—KB在肝细胞癌中的mRNA水平和蛋白活性度（0．152134±0．008024、216．73±12．36）均较癌旁组织（0．062129±0．004860、185．57±9．42）和正常肝组织（0．029771±0．002957、49．50±2．68）中显著增高（P〈0．05）；API-5的mRNA水平、tAPI-5和pAPI-5的蛋白水平在肝细胞癌（0．017701±0．002024、1．680000-4-0．298440、1．510000．4-O．299830）中显著高于癌旁组织（0．005069±0．000764、1．006300±0．233210、0．990000±0。175080）和正常肝组织（0．001500±0．000280、0．490000±0．122560、0．342700±0．071290）（P〈0．05）。NF—KB和API_5的mRNA水平随着Pim-2mRNA水平的变化而平行变化；tAPI-5和pAPI-5的蛋白水平及NF．KB活性度也随着Pim-2蛋白水平的变化而平行变化。结论在HCC中，Pim-2与API-5及NF—KB呈正相关，Pim-2、NF—KB及API-5的高表达可能与HCC的发生有关。

Objective To explore the expression and significance of proviral integration site of murine （Pim） -2 in hepatocellular carcinoma （HCC）. Methods HCC tissues and paired noncancerous liv- er tissues were collected from 27 cases of HCC admitted at the Second Affiliated Hospital of Chongqing Medical University, and normal liver tissues were obtained from surgically resected samples of 11 cases undergoing hepatic lobectomy at the same period. Then mRNA expression levels of Pim-2, nuclear factor-κB （NF-κB） and apoptosis inhibitor 5 （API-5）, the protein expression levels of Pim-2, tAPI-5 and pAPI-5, as well as NF-κB activity was detected by using real-time polymerase chain reaction （Real-time PCR）, Western blotting and electrophoresis mobility shift assay （EMSA）, and statistically analyzed. Results The expression levels of Pim-2 mRNA and protein （0. 129 676 ±0. 007 427 and 1. 300 000 ±0. 232 890） were significantly higher in HCC tissues than those in the controls （P 〈 0. 05 ）. The expression levels of NF-κB mRNA and protein （0. 152 134 ±0. 008 024, and 216. 73 ± 12.36） were significantly higher in HCC tissues than those in the controls （ P 〈 0. 05 ）. The expression levels of API-5 mRNA, and expression levels of tAPI-5 and pAPI-5 proteins （ 0. 017 701 ± 0. 002 024,1. 680 000 ±0. 298 440,1. 510 000 ±0. 299 830 ） were significantly higher in HCC tissues than those in the controls （ P 〈 0. 05 ）. The expression levels of NF-κB and API-5 mRNA, and the protein levels of tAPI-5 and pAPI-5, as well as NF-κB activity were just positively correlated with the level of Pim-2. Conclusion There was a positively correlation between the expression of Pim-2 with NF-κB and API-5 in HCC. The high expression of Pim-2, NF-κB and API-5 may be correlated with the occurrence and development of HCC.