人体肝癌发生过程中P27泛素—蛋白酶体降解相关因子的研究
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摘要
目的：研究肝细胞癌(HCC)发生过程中不同阶段细胞周期负调控因子P27蛋白泛素-蛋白酶体途径降解相关因子的表达及相互关系，以探讨HCC发生的分子生物学机制。方法：应用免疫组织化学方法检测正常肝组织、慢性肝炎、肝硬化、癌周肝硬化和肝癌共80例标本中的Cyclin E、Skp2和泛素表达情况，并用图像分析系统进行定量分析。结果：Cyclin E和泛素主要定位于胞核，Skp2蛋白在肝硬化、癌周肝硬化组主要定位于胞浆，肝癌组则以定位于胞核为主。三种蛋白的胞核表达均以肝癌组最强，明显高于其它各组(P＜0.05)，其中Cyclin E、Skp2蛋白表达从正常肝组织、肝硬化、癌周肝硬化到肝癌组有逐渐增强的趋势(Cyclin E阳性单位均值分别为20.8、22.8、27.5、48.6；Skp2阳性单位均值分别为15.8、23.7、29.5、48.2)，并且Cyclin E与肝癌分级成正相关关系(r=0.4468，P＜0.05)。慢性肝炎组Cyclin E、Skp2、泛素呈较高表达，仅次于肝癌组，且与正常肝组织、肝硬化、癌周肝硬化组间差异有统计学意义(P＜0.05)。三种蛋白核表达之间互成正相关关系。结论：肝癌发生过程中泛素-蛋白酶体途径降解增强可能是导致P27蛋白低表达的重要机制，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。Cyclin E表达与肝癌分级成正相关。
Objective: To investigate the expressions and correlations of three factors associated with the ubiquitin-mediated proteolysis of the p27 protein in human hepatocarcinogenesis, and to identify the molecular mechanism of hepatocarcinogenesis. Methods: By using immunohistochemistry, Cyclin E, Skp2 and Ubiquitin proteins were evaluated in the tissues of chronic hepatitis, liver cirrhosis, paratumor cirrhosis, HCC, and normal liver tissues (80 sample, totally). And the expressions of the three proteins were quantitatively measured by using Image Analysis System. Results: Mainly Cyclin E and Ubiquitin proteins locate in nucleus. There were two staining patters in the expression of Skp2 protein. One was nuclear staining patterns in HCC and chronic hepatitis, another was cytoplasmic staining in liver cirrhosis and paratumor cirrhosis. In nucleus, the expressions of these proteins were the highest in HCC, and proteins levels were noted to be higher in else groups (P<0.05). And from normal liver tissues, liver cirrhosis, paratumor cirrhosis to HCC, the expressions of Cyclin E and Skp2 protein were gradually increased. Respectively, in the four groups the means of Positive Unit were 20.8, 22.8, 27.5 and 48.6 (Cyclin E); 15.8, 23.7, 29.5 and 48.2 (Skp2). In HCC, the Cyclin E protein expression was positively correlated with histological grade (r=0.4468, P<0.05). Furthermore, in chromic hepatitis, the expressions of Cyclin E, Skp2 and Ubquitin proteins were only lower than those in HCC, and there were significant
Objective: To investigate the expressions and correlations of three factors associated with the ubiquitin-mediated proteolysis of the p27 protein in human hepatocarcinogenesis, and to identify the molecular mechanism of hepatocarcinogenesis. Methods: By using immunohistochemistry, Cyclin E, Skp2 and Ubiquitin proteins were evaluated in the tissues of chronic hepatitis, liver cirrhosis, paratumor cirrhosis, HCC, and normal liver tissues (80 sample, totally). And the expressions of the three proteins were quantitatively measured by using Image Analysis System. Results: Mainly Cyclin E and Ubiquitin proteins locate in nucleus. There were two staining patters in the expression of Skp2 protein. One was nuclear staining patterns in HCC and chronic hepatitis, another was cytoplasmic staining in liver cirrhosis and paratumor cirrhosis. In nucleus, the expressions of these proteins were the highest in HCC, and proteins levels were noted to be higher in else groups (P<0.05). And from normal liver tissues, liver cirrhosis, paratumor cirrhosis to HCC, the expressions of Cyclin E and Skp2 protein were gradually increased. Respectively, in the four groups the means of Positive Unit were 20.8, 22.8, 27.5 and 48.6 (Cyclin E); 15.8, 23.7, 29.5 and 48.2 (Skp2). In HCC, the Cyclin E protein expression was positively correlated with histological grade (r=0.4468, P<0.05). Furthermore, in chromic hepatitis, the expressions of Cyclin E, Skp2 and Ubquitin proteins were only lower than those in HCC, and there were significant
引文
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