NF-κBp65、Bcl-2、Bcl-xL蛋白在胰腺癌中的表达及其与P53和凋亡指数的关系  

Expression of NF-κBp65,Bcl-2,Bcl-xL and their relationships with expression of P53 proteins and apoptotic index in pancreatic cancer

作　　者：张克君[1] 李德春[1] 朱东明[1] 

机构地区：[1]苏州大学第一附属医院普通外科,江苏苏州215006

出　　处：《中国癌症杂志》2007年第2期105-109,共5页China Oncology

基　　金：卫生部科学研究基金资助(No:WKJ2004-2-001)

摘　　要：背景与目的:核因子κB通过调控下游bcl-2家族基因表达参入细胞凋亡调节过程,而p53除了参入细胞周期调节外也参入依赖bcl-2基因的细胞凋亡调控。在胰腺癌中NF-κBp65、Bcl-2和Bcl-xL蛋白表达与p53和凋亡的关系还不清楚。本研究系统地分析了核因子κBp65及其下游的bcl-2和bcl-xL抑凋亡基因在胰腺癌(PC)中的表达以及与P53蛋白表达和凋亡指数(AI)的关系。方法:免疫组化法检测25例胰腺导管腺癌(PC)和9例正常胰腺组织(NP)中P53蛋白表达;Western印迹法分析NF-κBp65蛋白表达;RT-PCR分析Bcl-2和Bcl-XL蛋白表达,TdT酶介导的原位缺口标记(TUNNEL)法了解胰腺癌细胞凋亡情况(AI)。结果:P53在PC组织阳性率(56%,14/25),高于NP组织阳性率(P<0.00);NF-κBp65、Bcl-2和Bcl-xL在PC组织表达相对值分别为:1.06±0.16、0.79±0.13、0.76±0.24,分别高于NP组织:0.23±0.016、0.23±0.074、0.18±0.026(分别P<0.05);14例p53阳性PC中,NF-κBp65、Bcl-2和Bcl-Xl表达相对值分别为:1.32±0.23、0.92±0.33、0.82±0.21;11例p53阴性PC中,NF-κBp65、Bcl-2和Bcl-xL表达相对值分别为:0.78±0.15、0.54±0.19、0.71±0.28(分别P<0.05,P<0.05,P>0.05);NF-κBp65和Bcl-2分别与P53表达有明显的正相关性(分别P<0.01,P<0.05),Bcl-xL与P53无相关性(P>0.05),NF-κBp65与Bcl-XL表达正相关(P<0.01),而NF-κBp65与Bcl-2表达无相关性(P>0.05);胰腺癌平均AI为(15.4±6.48)%,NF-κBp65表达与AI负相关(r=-0.297,P<0.05),而Bcl-2、Bcl-xL与AI无相关性(r=-0.203,P>0.05;r=-0.156,P>0.05)。结论:胰腺癌中抗凋亡因子表达上调,凋亡指数主要决定于NF-κBp65蛋白水平;NF-κBp65通过对下游bcl-xL基因表达的调控参与胰腺癌凋亡过程;p53在凋亡调节过程中起重要作用。Background and purpose： Members of the NF-kappaB family of transcription factors could activate bcl-2 anti-apoptotic genes at the transcriptional level and then regulate cell apoptosis. The p53 tumor suppressor gene has a clear role in both the regulation of cell cycle and expression of apoptosis-related bcl-2 family. There were few reports about the expression of NF-κBp65, bcl-2, bcl-xL and their relationships with p53 and cell apoptosis in pancreatic cancer. The present study was designed to analyze the expression of the antiapoptotic molecules nuclear factor kappaB（ NF-κBp65）, bcl-2 and bcl-xL in pancreatic ductal carcinoma （PC） and their correlations to the apoptosis index and p53 expression. Methods： Immunohistochemical analyses of P53 protein was performed on 25 cases of pancreatic ductal carcinoma and 9 cases of normal pancreas; Western blot was used to evaluate NF-κBp65 protein and RT-PCR for bcl-2 mRNA and bcl-xL mRNA of 25 cases of pancreatic ductal carcinoma and 9 NP cases. The apoptosis was determined by TUNEL. Results： The positive rate of P53 protein was 56% （14/25） in PC tissues, significantly higher than that in NP tissues（ P 〈 0.00）. The values of NF-κBp65, Bcl-2 and Bcl-xL in PC tissues were 1.06 ± 0.16, 0.79 ± 0.13, 0.76 ± 0.24 respectively, statistically higher than that in NP tissues with the value of 0.23 ± 0. 016, 0.23 ± 0. 074, 0.18 ± 0. 026 （ P 〈 0.05, respectively） ; In 14 PC cases with positive p53 expression, the values of NF-κBp65, Bcl-2 and Bcl-xL were 1.32 ±0.23, 0.92 ±0.33, 0.82 ±0.21, compared to the value of 0.78 ±0.15,0.54 ±0.19,0.71 ~0.28 for 11 PC cases with negative p53 expression, there were statistical differences in terms of the expression of NF-κBp65, Bcl-2（P 〈0.05） ; NF-κBp65 and Bcl-2 were correlated with P53 expression, respectively（r =0.379 P 〈0.01; r =0.284 P 〈0.05）, NF-κBp65 was also correlated with Bcl-xL expression（ r = 0.358, P 〈 0.05）, there was no correlation between p53 and Bcl-xl, NF-κBp65

关 键 词：胰腺癌 核因子κB BCL-2 bcl-xL P53 凋亡指数 

分 类 号：R73-3[医药卫生—肿瘤]