Low expression of DAB2IP contributes to malignant development and poor prognosis in hepatocellular carcinoma
- 14 December 2011
- journal article
- Published by Wiley in Journal of Gastroenterology and Hepatology
- Vol. 27 (6), 1117-1125
- https://doi.org/10.1111/j.1440-1746.2011.07049.x
Abstract
Background and Aim: DOC-2/DAB2 interactive protein gene (DAB2IP) is a novel member of the Ras GTPase-activating protein family and plays a tumor suppressive role in cancer progression, but its function in hepatocellular carcinoma (HCC) remains unclear. This aims of this study were to analyze the clinicopathological features of DAB2IP expression in HCC, and to determine the effect of DAB2IP on HCC cell behaviors in vitro. Methods: The expression of DAB2IP was detected in hepatocyte cell line and HCC cell lines by real-time reverse transcription-polymerase chain reaction and western blot. DAB2IP expression was then examined in 120 cases of clinical paraffin-embedded HCC tissue by immunohistochemistry (IHC). 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) method and in vitro invasive assay were finally performed to evaluate the effect of DAB2IP depletion on cell proliferation or invasion of HCC cells. Results: DAB2IP expression was lower in HCC cell lines or tissues than in hepatocyte cell lines, adjacent cirrhotic livers or normal livers (P < 0.05). Its expression was positively correlated with tumor size (P = 0.01). Patients with lower DAB2IP expression had shorter overall survival time (P = 0.013). DAB2IP suppresses proliferation and invasion of HCC cells in vitro. Conclusion: DAB2IP is a valuable marker for progression of HCC patients. Downregulation of DAB2IP is associated with poor prognosis in HCC patients. DAB2IP silence alone is sufficient to promote HCC cell proliferation and invasion in vitro.Keywords
This publication has 19 references indexed in Scilit:
- An oncogene–tumor suppressor cascade drives metastatic prostate cancer by coordinately activating Ras and nuclear factor-κBNature Medicine, 2010
- Role of DAB2IP in modulating epithelial-to-mesenchymal transition and prostate cancer metastasisProceedings of the National Academy of Sciences, 2010
- DAB2IP coordinates both PI3K-Akt and ASK1 pathways for cell survival and apoptosisProceedings of the National Academy of Sciences, 2009
- Differential expression of hDAB2IPA and hDAB2IPB in normal tissues and promoter methylation of hDAB2IPA in hepatocellular carcinomaJournal of Hepatology, 2007
- NORE1B, a candidate tumor suppressor, is epigenetically silenced in human hepatocellular carcinomaJournal of Hepatology, 2006
- Tumour lymphocytic infiltrate and recurrence of hepatocellular carcinoma following liver transplantationJournal of Hepatology, 2006
- Down-regulation of Human DAB2IP Gene Expression Mediated by Polycomb Ezh2 Complex and Histone Deacetylase in Prostate CancerJournal of Biological Chemistry, 2005
- Aberrant promoter methylation of human DAB2 interactive protein (hDAB2IP) gene in lung cancersInternational Journal of Cancer, 2004
- Differential Regulation of the Human Gene DAB2IP in Normal and Malignant Prostatic Epithelia: Cloning and CharacterizationGenomics, 2002
- The Mechanism of Growth-inhibitory Effect of DOC-2/DAB2 in Prostate CancerPublished by Elsevier BV ,2002