P53和Bcl-2家族蛋白在胰腺癌中的表达

Expression of apoptosis-related Bcl-2-family and P53 in human adenocarcinoma of the pancreas

目的:探讨胰腺癌组织(pancreatic carcinoma,PC)中P53和Bcl-2家族(Bcl-2,Bax,Bcl-xL,Bcl-xS)蛋白表达及与细胞凋亡的关系.方法:免疫组化法检测35例PC中P53蛋白表达,将PC分为P53阴性表达组(第1组,n=18)和P53阳性表达组(第2组,n=17);Western blot检测两组PC中P53,Bcl-2,Bax,Bcl-xL和Bcl-xS蛋白表达,TUNEL法检测第1组中凋亡指数(AI).结果:Bcl-2蛋白在P53阳性PC表达上调,而在P53阴性PC表达下调(P=0.047);Bax和Bcl-xL蛋白在两组PC中表达都明显上调(P=0.274,0.334);Bcl-xS在P53阳性表达PC明显下调,在P53阴性表达组明显上调(P=0.01);在P53阴性和阳性表达PC,AI分别为12.1±2.47和9.1±1.48(P=0.023);Bcl-2家族各成员表达与AI无相关性,而Bcl-2/Bax比率与AI有明显的相关性(P<0.01).结论:Bcl-2是依赖P53调节的抗凋亡蛋白,Bcl-xS是依赖P53调节的促凋亡蛋白,而P53主要通过调节Bcl-2/Bax比率发挥凋亡调节作用.

AIM： To investigate the relationships between P53 and Bcl-2 family （Bcl-2, Bax, Bcl-xL, Bcl-xS） expression and apoptosis in human pancreatic carcinoma （PC）. METHODS： The immunohistochemical method was used to detect the expression of P53 protein in a total of 35 patients with PC. The patients were divided into two groups, group I with immunonegative P53 （18 cases） and group 2 with immunopositive （17 cases）. The expressions of P53, Bcl-2, Bax, Bcl-xL, and Bcl-xS in both groups were detected by Western blot. The apoptosis index （AI） of group 1 was determined by terminal deoxynucleotidyltransferase-mediated UTP endlabeling （TUNEL）. RESULTS： Bcl-2 was remarkably up-regulated in group 2 but down-regulated in group 1 （P = 0.047）. Expressions of both Bax and Bcl-xL proteins were up-regulated in those two groups （P = 0.274, 0.334）. Bcl-xS was remarkably downregulated in group 2 but up-regulated in group1 （P = 0.01）. The AI of both groups were 12.1 ± 2.47 and 9.1 ± 1.48, respectively （P = 0.023）, no correlations were found between AI and expression of Bcl-2 family members, but marked correlations were noted between AI and the Bcl-2/bax ratios （P 〈 0.01）. CONCLUSION： Bcl-2 family is a group of anti- apoptotic proteins, and Bcl-xS is a pro-apoptotic protein. Both of them are dependent on the regulation of P53 which modulates apoptosis mainly through modifying Bcl-2/Bax ratios.