原发性肝癌信号转导途径相关抑癌基因

Tumor Suppressors of Cell Signaling Pathways in Hepatocellular Carcinoma

原发性肝癌(HCC)的发生发展是多基因参与、多基因相互作用的结果。抑癌基因通过信号途径发挥作用,其中包括:p53、Wnt、mTOR、RAS、Hedgehog等途径。30%～60%的肝癌中发现有p53突变,p53与p21、p27、p16等抑癌基因相互交叉,共同发挥抑癌作用。Wnt途径中,APC、Axin1及E-cadherin的编码基因在HCC中分别因高甲基化、突变、启动子超甲基化而失活。多数肝癌中都发现有mTOR的过度表达,mTOR途径受几个抑癌基因产物调控。RASSF1基因转录产物RASFF1A能与癌蛋白Ras相结合而影响细胞凋亡。

The development of hepatocellular carcinoma is a multi-gene-involved and multi-gene-interacted process.The activation of oncogene and the inactivation of suppressor gene are crucial events in the biological process of malignant changes in tumor cells.Studies have shown that suppressor genes play a role through signaling pathways.Here are five pathways having prominent tumor suppression activities involved in hepatocarcinogenesis,namely p53,Wnt,mTOR,RAS,and Hedgehog.p53 mutations have been found in 30-60% of liver cancers.p53 interacting with p21,p27 and p16 plays a tumor suppressor role together.In Wnt pathway,APC,Axin1 and E-cadherin,due to hypermethylation,mutation and promoter hypermethylation,are respectively inactivated in HCC.Over-expression of mTOR has been found in most liver cancers.mTOR pathway is regulated by several tumor suppressors.RASFF1A,a RASSF1 gene transcriptor,can affect normal apoptosis by binding to Ras protein.With the development of the research into signalling pathways and hepatocarcinogenesis,the roles of various tumor suppressors is further clarified.Identification of tumor suppressor activity in signalling pathways will further develop the theories of hepatocarcinogenesis and suggest a promising future for gene diagnosis and gene therapy strategy.