Role of the pituitary tumor transforming gene 1 in the progression of hepatocellular carcinoma
Role of the pituitary tumor transforming gene 1 in the progression of hepatocellular carcinoma
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DOI：
10.4161/cbt.11.3.14102
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发表时间：
2011-02-01
影响因子：
3.6
通讯作者：
Lv, Shulan
中科院分区：
文献类型：
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作者：
Liang, Ming;Chen, Xianfeng;Lv, Shulan
为了论证垂体肿瘤转化基因1（PTTG1）在肝细胞癌（HCC）发生发展中的作用及其作为癌症治疗分子靶点的价值，我们分析了PTTG1 mRNA和蛋白的表达及其与HCC临床病理特征和碱性成纤维细胞生长因子（bFGF）表达的关系。观察到癌组织中PTTG1 mRNA水平和PTTG1蛋白阳性率均显着高于癌旁非癌组织（均p < 0.001）。 PTTG1蛋白水平与多种临床病理参数相关，包括甲胎蛋白水平、门静脉肿瘤血栓形成、肿瘤分期和bFGF蛋白水平（p < 0.05）。与未转染的对照相比，转染PTTG1 siRNA的HepG2和SMMC-7721细胞的增殖指数显着降低，凋亡率显着升高。 siRNA敲低PTTG1表达后，HepG2和SMMC-7721细胞中Caspase-3、Bax、p21和p53的表达显着增加。总之，PTTG1基因在HCC患者的癌组织中表达上调，并参与HCC的进展。抑制PTTG1表达可降低肝癌细胞系的细胞增殖并诱导细胞凋亡，表明PTTG1可能成为HCC治疗的新治疗靶点。
In order to demonstrate the role of the pituitary tumor transforming gene 1 (PTTG1) in the development of hepatocellular carcinoma (HCC) and its value as a molecular target for cancer therapy, we analyzed the expression of PTTG1 mRNA and protein, and their relation to clinicopathological characteristics and basic fibroblast growth factor (bFGF) expression in HCC. It was observed that the level of PTTG1 mRNA and the positive rate of PTTG1 protein in cancerous tissues were significantly higher than that in adjacent non-cancerous tissues (both p < 0.001). The PTTG1 protein levels were correlated with several clinicopathological parameters, including alpha-fetoprotein level, portal vein tumor thrombosis, tumor stage and bFGF protein level (p < 0.05). The proliferation indices were significantly less and the apoptotic rates were significantly higher in the HepG2 and SMMC-7721 cells treated with PTTG1 siRNA transfection than their untransfected counterparts. The expressions of Caspase-3, Bax, p21 and p53 in HepG2 and SMMC-7721 cells were significantly increased after siRNA knockdown of PTTG1 expression. In conclusion, the PTTG1 gene is upregulated in the cancerous tissue from patients with HCC and involved in the progression of HCC. Inhibiting PTTG1 expression decreases cell proliferation and induces apoptosis in hepatic cancer cell lines, indicating that PTTG1 may be a new therapeutic target for HCC treatment.