【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。更多还原

【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.更多还原