TGF-β/SMADS通路及其Smad4基因在胃癌中的研究现状

Research Status of TGF-β/SMADS Transduction Pathways and Smad4 Gene in Gastric Cancer

转化生长因子β(TGF-β)/SMADS信号转导通路在肿瘤发生机制中发挥重要作用。近年来,许多研究表明了TGF-β超家族的配体、受体、SMAD蛋白、上游和下游调节因子与多种信号通路间的相互对话在不同肿瘤中的作用机制。Smad4基因是TGF-β信号转导系统的重要中间环节,其失活在人类肿瘤中占很高比例,可导致多种肿瘤的发生、发展。目前认为,Smad4基因的蛋白失活主要与该基因的缺失、突变和甲基化有关。突变包括无义突变、错义突变和移码突变等;缺失包括单等位基因杂合性缺失和双等位基因纯合性缺失。

Transformation growth factor β （TGF-beta）/SMADS signal transduction pathways play an important role in tumorigenesis. In recent years, many studies have revealed the TGF-β superfamily ligand and receptors,SMAD proteins, upstream and downstream regulatory factors and a variety of signal paths be- tween the interactive dialog in the related mechanism of the tumor. Smad4 gene is an important intermediate link of TGF-β signal transduction system, its inactivation accounts for a high proportion in human cancer, which can lead to a variety of tumorigenesis development. Now it＇s considered that Smad4 protein inactivation is mainly correlated with the gene mutations,loss, and methylation. Mutation includes nonsense mutation, mis- sense mutation and frameshift mutations;loss includes single allele heterozygosity missing and double allele homozygosity missing.