垂体瘤转化基因1(PTTG1),也被称为分离酶抑制蛋白基因,是近几年从大鼠垂体肿瘤中发现的癌基因.它不但可以与分离酶结合,使分离酶失活,从而抑制姐妹染色单体的分离,还具有转录激活活性.已有的染色质免疫共沉淀结合芯片数据显示,PTTG1不仅可以直接调控基因的转录,也可以与其他蛋白,如PTTG1结合因子(PBF)、p53、Sp1、上游刺激因子1(USF1)等相互作用来调控下游基因的转录.在NIH 3T3细胞中,PTTG1激活c-Myc的转录,增强NIH 3T3细胞在裸鼠体内的成瘤能力.PTTG1也能激活肿瘤细胞中成纤维细胞生长因子2(FGF2)的转录,从而促进肿瘤血管生成.PTTG1结合p53、抑制p21表达、激活周期蛋白D3的能力,提示它在凋亡、细胞周期和衰老方面也发挥作用.另外,PTTG1在肿瘤转移和肝癌的发生发展中也发挥着重要作用.我们简要综述了PTTG1的靶基因,及其在肝癌及肿瘤转移中的研究进展.%Pituitary tumor-transforming gene-1(PTTG1), also named securin, is a transforming gene first discov⁃ered in rat pituitary tumor cells. Not only dose it have securin functions, but also possesses transcriptional activi⁃ty. Chromatin immunoprecipitation-on-chip(ChIP-on-chip) study revealed that PTTG1 is a global transcription fac⁃tor, which exerts its transcriptional activity either by directly binding to DNA or by interacting with other known transcription factors including PTTG1 binding factor(PBF), p53, Sp1, and upstream stimulatory factor 1(USF1). PTTG1 has several validated transcriptional targets that are involved in diverse cellular processes. PTTG1 activates c-Myc in NIH 3T3 cells, suggesting a role in cell transformation. PTTG1 induces the expression of fibroblast growth factor 2(FGF2) and promotes tumor angiogenesis. It binds to and inhibits p53 transcriptional activity. PTTG1 activates cyclin D3 and represses p21 expression, indicating a role in cell cycle regulation and cell senes⁃cence. Hence, we reviewed PTTG1 and its transcriptional targets, and discussed their implications in tumor devel⁃opment and metastasis, especially in the context of hepatocellular carcinoma.
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