Fujii Tsutomu, Nomoto Shuji, Koshikawa Katsumi, Yatabe Yasushi, Teshigawara Osamu, Mori Toshiaki, Inoue Soichiro, Takeda Shin, Nakao Akimasa
Department of Surgery II, Graduate School and Faculty of Medicine, Nagoya University, Nagoya, Japan.
Hepatology. 2006 Jun;43(6):1267-75. doi: 10.1002/hep.21181.
The pituitary tumor transforming gene 1 (PTTG1) protein is cell-cycle regulated and is identified as a human securin that inhibits sister chromatid separation and is involved in transformation and tumorigenesis. PTTG1 has very low or undetectable expression in most normal human tissues, but it is abundantly expressed in malignant cell lines and pituitary tumors. In this study, we investigated human PTTG1 expression in 62 hepatocellular carcinoma (HCC) specimens using quantitative real-time reverse transcription polymerase chain reaction analysis. We found that, compared with corresponding noncancerous liver tissues, PTTG1 was remarkably overexpressed in HCCs (PTTG1/beta-actin; 0.443 +/- 0.073 vs. 0.068 +/- 0.007; P < .0001). Furthermore, we found a significant correlation between PTTG1 expression and serum alpha-fetoprotein level (P < .001). Univariate and multivariate analyses revealed that the PTTG1 messenger RNA (mRNA) expression was an independent prognostic factor for disease-free (odds ratio 2.70; P = .037) and overall (odds ratio 5.35; P = .007) survival. Moreover, we discovered a significant relationship between PTTG1 expression and intratumoral microvessel density. Our data supported an important role for PTTG1-mediated upregulation of fibroblast growth factor (FGF)-2, one of angiogenesis and modulation of tumor progression, in hepatocarcinogenesis. In conclusion, PTTG1 might be critically involved in the development of HCCs through the promotion of angiogenesis. PTTG1 is overexpressed in HCC and our results suggest that PTTG1 mRNA expression has prognostic significance for the survival of postoperative patients with HCC.
垂体肿瘤转化基因1（PTTG1）蛋白受细胞周期调控，被鉴定为一种人类分离酶抑制蛋白，可抑制姐妹染色单体分离，并参与细胞转化和肿瘤发生。PTTG1在大多数正常人体组织中表达极低或无法检测到，但在恶性细胞系和垂体肿瘤中大量表达。在本研究中，我们采用定量实时逆转录聚合酶链反应分析，检测了62例肝细胞癌（HCC）标本中人类PTTG1的表达。我们发现，与相应的癌旁肝组织相比，PTTG1在肝癌中显著过表达（PTTG1/β-肌动蛋白；0.443±0.073对0.068±0.007；P<0.0001）。此外，我们发现PTTG1表达与血清甲胎蛋白水平之间存在显著相关性（P<0.001）。单因素和多因素分析显示，PTTG1信使核糖核酸（mRNA）表达是无病生存（比值比2.70；P=0.037）和总生存（比值比5.35；P=0.007）的独立预后因素。此外，我们发现PTTG1表达与瘤内微血管密度之间存在显著关系。我们的数据支持PTTG1介导的成纤维细胞生长因子（FGF）-2上调在肝癌发生中的重要作用，FGF-2是血管生成和肿瘤进展调节的因子之一。总之，PTTG1可能通过促进血管生成在肝癌的发生发展中起关键作用。PTTG1在肝癌中过表达，我们的结果表明PTTG1 mRNA表达对肝癌术后患者的生存具有预后意义。
