肝癌发生过程中转录因子AP-1活化的研究

Activation of AP-1 Transcription Factor on the Duration of Hepatocarcinogenesis

目的:检测肝癌及其癌周组织中AP-1活化状态,探索该转录因子在肝癌发生过程中可能的作用。方法:用电泳迁移率转移试验、免疫印迹和RNA酶保护性分析等方法,测定15例原发性肝癌及其癌周组织中AP-1与DNA的结合活性、AP-1复合物的蛋白组成以及细胞增殖状况。结果:与正常肝组织相比,AP-1与DNA结合活性在73%的癌周组织中增高;60%的肝癌组织中AP-1结合活性比癌周组织进一步增高;其AP-1二聚体主要由JunD、c-Jun和c-Fos蛋白参与组成,AP-1结合活性与JunD和c-Jun蛋白表达水平呈正相关。结论:AP-1的激活是肝癌发生过程中的早期频发事件,可能有助于肝细胞恶性转化表型的获得,在肝癌的形成中具有重要作用。

Objective: To explore the potential effect of AP-1 transcripti on f actor on the duration of hepatocarcinogenesis by investigating its activation in the hepatic cancer and peri-cancerous tissues of the liver. Methods: Electroph oretic mobility shift assay (EMSA), Western blot and Ribonuclease protection ass ay(RPA) were used to measure the DNA binding activity of AP-1, the composition of AP-1 proteins and cell proliferation respectively in the hepatic carcinoma a nd its surrounding of 15 primary liver cancers. Results: AP-1 binding activity was elevated in the peri-cancerous tissue, compared with histology normal liver s, from 73%of all cases. A further activation of AP-1 binding in the hepatic c ancer was detected in 60%of the cases. AP-1 dimers were formed by the particip ation of JunD, c-Jun and c-Fos proteins.AP-1 binding activity at the hepatic cancer was positively related to the expression of JunD and c-Jun. Conclusion: The activation of AP-1 transcription factor is a frequent and early event in hu man hepatocellular carcinomas. It contributes probably to the acquisition of a t ransformed cell phenotype during hepatocarcinogenesis.