【摘要】 目的探讨HCC发生过程中P27蛋白低表达的调节机制.方法应用免疫组织化学方法检测正常肝组织、非癌周肝硬化、癌周肝硬化和肝癌各20例标本中P27、Cyclin E、Skp2和泛素的表达及定位,并用图像分析系统进行定量分析.结果P27、Skp2定位于胞核和/或胞浆,CyclinE和泛素主要定位于胞核.P27蛋白胞核表达(从正常肝组织、肝硬化、癌周肝硬化到肝癌组阳性单位PU均值分别为30.1、30.5、27.3、21.6)在肝癌组中最弱,明显低于除癌周肝硬化外的其它各组(P<0.05).胞核中CyclinE(PU:20.8、22.8、27.5、48.6)、Skp2(PU:15.8、23.7、29.5、48.2)和泛素(PU:33.1、38.1、37.5、51.7)三种蛋白的表达均以肝癌组最强,明显高于其它各组(P<0.05).Cyclin E、Skp2、泛素三种蛋白核表达之间互成正相关关系,P27蛋白与Cyclin E(r=-0.2718,P<0.01)、P27蛋白与Skp2(r=-0.2739,P<0.01)成负相关关系.Skp2胞浆表达、肝癌组与癌周肝硬化组及非癌周肝硬化组之间的差异有统计学意义(P<0.05).结论肝癌发生过程中泛素-蛋白酶体途径降解增强可能导致P27蛋白低表达,而其降解可能需要以Skp2蛋白核输入相关因子的作用发挥为前提.Skp2蛋白高表达可能是先于P27低表达发生的事件.更多还原

【Abstract】 Objective Toinvestigate the regulatingmechanism of the expressions of P27 protein in HCC. Methods The expressions of P27,Cyclin E,Skp2 and Ubiquitin proteins in normal liver,non-paratumor cirrhosis, paratumor cirrhosis and HCC tissues ( 20 specimens per group) were detected by immunohistochemistry, and quantitatively analyzed by Image Analysis Software. Results Cyclin E and Ubquitin were mainly located in nuclei; P27 and Skp2 were located in nuclei and/or cytoplasm. In nuclei,theexpression of P27 was the lowest in HCC.Respectively,in the four groups from normal to HCC,the means of Positive Unit (PU) were 30.1, 30.5, 27.3 and 21.6.Except paratumor cirrhosis, there were significant differences between the expression of P27 in HCC and that in else groups (P <0.05). Cyclin E (PU: 20.8,22.8,27.5 and 48.6),Skp2 (PU: 15.8,23.7,29.5 and 48.2) and Ubiquitin (PU: 33.1,38.1, 37.5 and 51.7) were the highest in HCC (P<0.05), In nuclei, Cyclin E, Skp2 and Ubiquitin were positively correlated with each other,while P27 was inversely correlated with Cyclin E (r=-0.2718,P<0.01) and Skp2 (r=-0.2739,P<0.01). In cytoplasm,there were significant differences between the expression of Skp2 in HCC and that in non-paratumor cirrhosis or paratumor cirrhosis (P<0.05).Conclusions Our study indicates that the increase of the ubiquitin-mediated proteolysis may account for the decrease of the expressions of P27 in HCC. The overexpression of Skp2 protein may occur before the decrease or loss of P27 protein,and then enter the nuclei and make the proteolysis of the P27 possible,with important implications for the pathogenesis of HCC.更多还原