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肝细胞癌组织中Skp2的表达及与p27kip1、PCNA蛋白表达的关系
引用本文:程阳,王酉,陈莉,陆牡丹,秦军,崔小鹏,李鹏,刘胜利. 肝细胞癌组织中Skp2的表达及与p27kip1、PCNA蛋白表达的关系[J]. 南通医学院学报, 2007, 27(3): 160-163
作者姓名:程阳  王酉  陈莉  陆牡丹  秦军  崔小鹏  李鹏  刘胜利
作者单位:1. 南京港口医院普外科,南京,210011;东南大学附属中大医院普外科
2. 南通大学医学院病理解剖学教研室
3. 南通大学附属医院
4. 东南大学附属中大医院普外科
基金项目:国家自然科学基金;江苏省自然科学基金;江苏省高校自然科学基金;江苏省高校自然科学基金;江苏省科技指导性计划;六大人才高峰第二批项目资助计划;江苏省卫生厅科研项目
摘    要:目的:探讨Skp2的表达在肝细胞癌(HCC)发生发展中的作用,及其与p27kip1(p27)和PCNA的关系。方法:收集76例HCC及癌旁组织,l0例肝血管瘤旁肝组织的临床病理档案资料,l0例HCC及癌旁肝新鲜组织,采用免疫组织化学方法及免疫印迹技术检测Skp2、p27及PCNA蛋白在这些组织中的表达。结果:免疫印迹结果显示:Skp2在HCC组织中的表达明显高于对应的癌旁肝组织。免疫组织化学结果显示HCC中Skp2的阳性率(24.08%)显著高于癌旁组织和正常肝组织(P<0.001)。Skp2的表达与肝癌组织分化程度,血清AFP值及转移有关(P<0.05)。p27在正常肝组织和癌旁组织中的表达明显高于HCC组织(P<0.001)。HCC组织中PCNA蛋白的表达明显高于癌旁和正常组织(P<0.01)。HCC组织中Skp2的表达与p27呈负相关(P<0.001);与PCNA呈正相关(P<0.01)。结论:Skp2在HCC组织中表达是上调的,可能是通过作用于细胞周期调控蛋白p27,加速了对p27泛素化依赖的蛋白降解,使其表达及代谢发生异常。导致细胞周期失控并促进细胞异常增殖,从而参与了HCC的发生和发展。

关 键 词:肝细胞癌  免疫印迹法  免疫组织化学  增殖细胞核抗原  Skp2  P27
文章编号:1000-2057(2007)03-0160-04
修稿时间:2007-03-16

Expression of Skp2 in hepatocellular carcinoma and its relationship with p27kip1 and PCNA protein expressions
CHEN Yang, WANG You, CHEN Li, et al. Expression of Skp2 in hepatocellular carcinoma and its relationship with p27kip1 and PCNA protein expressions[J]. ACTA Academiae Medicinae Nantong, 2007, 27(3): 160-163
Authors:CHEN Yang   WANG You   CHEN Li   et al
Affiliation:1.Department of General Surgery, Gang Kou Hospital, Nanjing 210011; 2.Department of General Surgery, Zhong Da Hospital, Southeast University; 3.Department of Pathology, Nantong University; 4. the Affiliated Hospital of Nantong University, Nantong 226001
Abstract:Objective:To investigate the expression of Skp2 and its relationship with expressions of p27 and PCNA proteins in human hepatocellular carcinoma(HCC). Methods: Immunohistochemical study for Skp2,p27, PCNA was performed on 10 cases of native liver tissue adjacent to hepatic hemangioma and in 76 cases of hepatocellular carcinoma tissues and adjacent nontumorous tissues. Fresh specimens from 10 cases of HCC and the adjacent liver tissue were also collected for Western blot analysis. Results: Western blot analysis showed that Skp2 expressions in HCC was higher than those in adjacent liver tissue. Immunohistochemistry of 76 HCCs showed marked increase in Skp2 and PCNA expressions but not p27, in HCC compared with noncancer tissues. Skp2 expression in HCC correlated with histological differentiation, serum alpha-fetal protein levels and metastasis (P<0.05). In HCC, inverse correlation was found between Skp2 and p27(P<0.01) and a positive correlation was found between Skp2 and PCNA(P<0.01). Conclusions: Expression of Skp2 is up-regulated significantly in HCC compared with adjacent liver tissue and normal liver tissues,and overexpression of Skp2 reduces the protein level of p27 through ubiquitin-dependent degradation and causes disruption of cell cycle control and enhancement of the proliferative activity, indicating Skp2 playes an important role in oncogenesis and development of HCC.
Keywords:Hepatocellular carcinoma  Immunoblotting  Immunohistochemistry  Proliferating cell nuclear antigen  Skp2  P27
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