Overexpression of pituitary tumor transforming gene 1 in HCC is associated with angiogenesis and poor prognosis

Abstract

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/␤-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 ( H epatocellular carcinoma (HCC) is a common cancer worldwide, especially in Southeast Asia and Africa, and it is the third leading cause of death from malignant disease in Japan. 1 Surgical treatments including hepatic resection and liver transplantation improve the chances of survival for a patient with HCC. However, most patients experience recurrence or metastasis after surgery, and their prognosis remains poor. 2 Therefore, to further improve patient survival, identifying genetic markers of recurrence or metastasis of HCC is important.Recent developments in microarray technology have ushered in a new era in medical science, allowing precise identification of the genetic factors associated with various tumors. [3][4][5] Ramaswamy et al. 6 reported that 17 genes were associated with metastasis in several primary solid tumors and that the pituitary tumor transforming gene 1 (PTTG1) protein was one of them. PTTG1 was originally isolated from cloned rat GH4 pituitary tumor cells, 7 and its human homolog hpttg was cloned from a thymus cDNA library. 8 It is identified as a human securin that inhibits sister chromatid separation and is involved in malignant transformation and tumorigenesis. 9 At the end of metaphase, securin is degraded by an anaphase promoting complex, releasing tonic inhibition of separin, which in turn mediates the degradation of cohesions, the proteins that hold sister chromatid together. Overexpression of the undegradable PTTG1 disrupts the sister chromatid

Polymorphisms in mitotic checkpoint-related genes can influence survival outcomes of early-stage non-small cell lung cancer

“…Alternatively, overexpression of mitotic checkpoint genes may result in defective mitotic checkpoint function [22]. Associations between the overexpression of mitotic checkpoint genes and poor prognosis have been reported in several cancers [23][24][25][26][27]. In the present study, a higher level of BUB3 expression was observed in lung tumor, and worse OS in patients with the BUB3 rs7897156TT genotype was observed.…”

Pituitary tumor transforming gene 1 in the liver

“…All of our findings demonstrate broader PTTG-1 expression in the liver than that reported by Fujii et al 1 Furthermore, on the basis of the above microscopic observations, it is possible to say:…”

“…We read with interest and appreciate the paper by Fujii et al, 1 but feel it is necessary to make the following observations.…”

Proliferation marker securin identifies favourable outcome in invasive ductal breast cancer

“…Prognostic associations of securin have been reported in gliomas, and in hepatocellular, thyroid and esophageal carcinomas (Shibata et al, 2002;Fujii et al, 2006;Genkai et al, 2006). We have previously described securin expression in a set of genes aberrantly expressed in colorectal carcinoma as compared to paired control samples from normal mucosa (Talvinen et al, 2006) where securin expression was upregulated both at mRNA and protein levels.…”