PKC信号通路在实验性肝癌发生过程中的变化特征及与卵圆细胞增殖转化的关系  

Expressional Characteristics of Protein Kinase C (PKC) Signal Transduction System and Their Relationships with Proliferation and Transformation of Oval Cells in Experimental Hepatocarcinogenesis

作　　者：向锦[1] 吴秋良[1] 陈琼荣[2] 匡亚玲[1] 陈健智 赵国强[4] 

机构地区：[1]华南肿瘤学国家重点实验室//中山大学肿瘤防治中心病理科,广东广州510060 [2]湖北省肿瘤医院病理科,湖北武汉430000 [3]广东南海市人民医院病理科,广东南海528200 [4]中山大学病理学教研室,广东广州510089

出　　处：《中山大学学报（医学科学版）》2009年第A04期28-33,共6页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家自然科学基金(30170473);广东自然科学基金(04009326);广州市科技计划项目(2004J1-C0271)

摘　　要：【目的】探讨实验性肝癌发生、发展过程中PKC-α和C-Jun的表达与卵圆细胞生长之间的关系。【方法】用诱癌剂3-甲基-4-甲基氨偶氮苯(DAB)饲喂SD大鼠构建肝癌模型,分别用斑点杂交检测PKC-α mRNA及用Northen Blot检测C-Jun mRNA在肝癌发生过程中几个阶段(第4周、第8周、第14周、第17周、第24周)的表达,并用薄层色谱仪线性扫描进行半定量。【结果】在第4周,诱癌组肝脏汇管区出现少量卵圆细胞,同时诱癌组肝脏可检测到PKC-α和C-Jun mRNA的表达。更有意义的是,诱癌组PKC-α和C-Jun mRNA的表达强度及卵圆细胞的数量随着实验的进程从第8周开始急剧增加,持续经过第14周并在第17周达到高峰,然后开始下降,同时在第17周出现不典型增生的卵圆细胞及多灶性肝细胞癌和胆管上皮细胞癌。在第24周,诱癌组肝脏出现大片肝细胞癌和胆管上皮细胞癌,但几乎看不到正常和不典型增生的卵圆细胞,同时PKC-α和C-Jun mRNA的表达强度急剧减弱,因此,在整个诱癌过程中,PKC-α和C-Jun mRNA表达的变化曲线与卵圆细胞的增殖及恶性转化基本一致。【结论】在实验性肝癌发生过程中卵圆细胞可能是肝癌的始动细胞,PKC-α和C-Jun在卵圆细胞的增殖和恶性转化中发挥重要的作用,并由此推测PKC-α和C-Jun的过表达是肝癌形成的前期事件。[ Objective ] Oval cells which posses the properties of stem cell/progenitors of liver have been found to be related to hepatocarcinogenesis. PKC-α and C-Jun have multiple effects on cell proliferation, differentiation, and transformation. This study was to explore the correlations of PKC-α, C-Jun and oval cells in the process of hepatocarcinogenesis. [Method] An animal model of experimental hepatocarcinoma by feeding SD mice with 3＇-me-DAB was established. The expression characteristics of PKC-α, C-Jun were detected by Dot-blot and Northern blot hybridization in 5 intervals （4-, 8-, 14-, 17-, and 24-week） during hepatocarcinogenesis. The semi-quantitative estimation for the expression level was performed by lining scan using thin-layer chromatography （TLC）. [Result] A small number of oval cells could initially be found in liver tissue of SD mice feed with 3＇-me- DAB for 4 weeks, and the expression of PKC-α mRNA and C-Jun mRNA was also detected simultaneously. Meaningfully, the PKC-α mRNA and C-Jun mRNA expression intensity and the quantity of oval cells were both increasing from the 8th through 14^th to 17a week and then decrease. The dysplastic oval cells and multiple hepatocarcinoma foci were formed in the 17^th mice. No normal and dysplastic oval cells were found in the 24^th mice; while the PKC-α mRNA and C-Jun mRNA expression intensity was decreased significantly. So the expression curve of PKC-α mRNA and C-Jun mRNA coincided with that of oval cell proliferation and its malignant transformation during experimental hepatocarcinogenesis. [Conclusion] The oval cells could be recognized as progenitor cells of hepatocarcinoma. The overexpression of PKC-α and C-Jun plays an important role in oval cell proliferation and then malignant transformation. Accordingly, the PKC-α and C-Jun overexpression is an event before the formation of hepatocarcinoma.

关 键 词：肝肿瘤 卯圆细胞 PKC-Α C—Jun 干细胞/定向干细胞 

分 类 号：R735.7[医药卫生—肿瘤]