DLC-1与肝癌关系研究

DLC-1基因是一种肿瘤抑制基因,位于人类染色体8p21．3-22。它是RhoA特异性GTP酶的激动蛋白,与调控细胞增殖和粘附的信号传导通路关系密切,在人类多种肿瘤中呈低表达或表达缺失。研究发现DLC-1基因在原发性肝癌(HCC)及肝癌细胞系中表达缺失,提示该基因在原发性肝癌中抑制了肝癌细胞的增殖。DLC-1表达的恢复引起了caspase-3介导的细胞凋亡,抑制肝癌细胞的生长和癌细胞的浸润,从而在肝细胞癌的转移、侵袭及肿瘤细胞的生物特性方面发挥作用。因其与肝癌发生,转移乃至复发关系密切,使其在肝癌早期发现,早期预测肝癌的转移复发及肝癌的预后方面发挥重要角色。

Study on the Relationship Between DLC-1 and Hepatocellular Carcinoma

Deleted in liver cancer 1(DLC-1),which is a tumor suppressor gene,is located at human chromosome 8p21.3-22.It functions as a GTPase activating protein for RhoA,and may be involved in signal transduction pathways which regulate stress fiber and focal adhesion assembly.Low or absent expression of DLC-1 gene could be found in many kinds of human tumors.It is frequently inactivated due to genomic deletion or promoter hypermethylation in transformed cells,and its overexpression can result in the inhibition of colony formation,cell migration and suppression of tumor formation.That loss of heterozygosity was detected for DLC-1 in primary hepatocellular carcinomas and in HCC cell lines suggests that DLC-1 inhibits cell growth in human hepatocellular carcinoma cells.The restoration of DLC-1 expression in HCC cells results in caspase-3- mediated apoptosis,inhibition of cell growth and invasiveness,as well as in reduction of the ability of the cells to form tumors, which is associated with cell proliferation,morphology,and migration in human hepatocellular carcinoma.Because of the significant correlation of the expression of DLC-1 to growth,metastasis,or recurrence of the bepatocellular carcinoma,DLC-1 gene may play an important role in the early discovery and prediction,recurrence and prognosis of hepatocellular carcinoma.