Expression of c-erbB-2 and glutathione S-transferase-pi in hepatocellular carcinoma and its adjacent tissue

Zhaoshan, Niu; Wang, Mei

doi:10.3748/wjg.v11.i28.4404

Cited by 20 publications

(16 citation statements)

References 25 publications

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“…Other consequences of the genetic polymorphisms were also investigated, which included the difference in tolerance to toxic agents due to varied expression of GST isoforms 30. In the present study, the upregulation of GST proteins might be related to their roles of detoxification during the pathogenesis of HCC 31. During hepatocarcinogenesis, GSTs are believed to involve in promoting drug resistance to anti‐cancer therapy.…”

Section: Discussionmentioning

confidence: 81%

Two‐dimensional differential gel electrophoresis/analysis of diethylnitrosamine induced rat hepatocellular carcinoma

Chen

Chan

et al. 2008

Intl Journal of Cancer

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Diethylnitrosamine (DEN) is a known carcinogen that can alkylate DNA molecules. In rats, DEN-induced hepatocellular carcinoma (HCC) model is well established. In this study, we used a twodimensional differential gel electrophoresis (2D-DIGE) system and liquid chromatography/mass spectrometry/mass spectrometry to identify the differential expression protein profiles between the DEN-induced HCC and healthy liver cells. Western blotting and semiquantitative RT-PCR were used to further confirm the results. Seventeen differentially expressed spots were identified in DEN-induced HCC cells. Among all, the most prominent upregulated proteins include the members of the glutathione Stransferase super family, aldo-keto reductase superfamily and proteins involved in the response to oxidative stress. Downregulation was observed in 2 proteins that were known to contribute to hepatic dysfunction. This study provides the first comprehensive protein profiling of the DEN-induced HCC in rats. This model simulates the differential protein expression of human HCC and may be useful for further understanding the mechanism of HCC tumorigenesis. ' 2008 Wiley-Liss, Inc.Key words: hepatocellular carcinoma; diethylnitrosamine; twodimensional differential gel electrophoresis; glutathione S-transferase Hepatocellular carcinoma (HCC) is a major malignancy worldwide.1 It is the fourth most common malignant tumor in the world 2 and is the second leading fetal disease in Mainland China. 3 In last 2 decades, the incidence of HCC has increased substantially all over the North America and Europe. 4 Studies have indicated HCC is associated with a major risk factor of hepatitis B and C viral infections [i.e., hepatitis B virus (HBV) and hepatitis C virus (HCV)].5 However, other factors such as aflatoxin B1 exposure, alcohol drinking and genetic defects have also aroused research interests in recent years. 6,7 To further understand the disease, animal models have been established for the study of hepatocarcinogenesis. These include the two-stage initiation-promotion 8 and the three-stage initiation, promotion and progression 9 models. The initiative period is characterized by the mutation of cells, which then undergo tumor promotion via active cell division or altered genome expression induced by chemicals.10 Thereafter, mutations continue and lead to the development of HCC cells via a number of causes such as the presence of HBV, HCV or radiation. Changes such as oxidation, chemical adducts and errors in the DNA bases and repair are also implicated in the early cellular changes.11 They are the crucial changes in the initial stage of HCC, which correspond to the histological observations including fibrosis, cirrhosis, and hepatocellular adenoma. 11In this study, diethylnitrosamine (DEN) was employed to induce HCC in rats. It is an environmental carcinogen and a hepatotoxin. It is commonly used in inducing hepatocarcinogenesis as it causes degenerative, proliferative and neoplastic lesions in the liver. DEN is a chemical agent that can alkylate DNA mo...

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Section: Discussionmentioning

confidence: 81%

Two‐dimensional differential gel electrophoresis/analysis of diethylnitrosamine induced rat hepatocellular carcinoma

Chen

Chan

et al. 2008

Intl Journal of Cancer

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“…The high prevalence of methylation in normal liver could be attributable to the fact that only low levels of GSTP1 mRNA are found in adult liver (http://symatlas.gnf.org/SymAtlas/, accessed October 7, 2007), 40 and immunohistochemical analysis demonstrated that expression of the protein is restricted to bile duct epithelial cells whereas other cells types of the liver do not have detectable levels of the protein. 31,41 GSTP1 might therefore become partially methylated. A second possibility would be that the methylation could also be attributable to aging.…”

Section: Discussionmentioning

confidence: 99%

Rapid Identification of Promoter Hypermethylation in Hepatocellular Carcinoma by Pyrosequencing of Etiologically Homogeneous Sample Pools

Dejeux

Audard

Cavard

et al. 2007

The Journal of Molecular Diagnostics

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Aberrant DNA methylation patterns have been identified in a variety of human diseases, particularly cancer. Pyrosequencing has evolved in recent years as a sensitive and accurate method for the analysis and quantification of the degree of DNA methylation in specific target regions. However, the number of candidate genes that can be analyzed in clinical specimens is often restricted by the limited amount of sample available. Here, we present a novel screening approach that enables the rapid identification of differentially methylated regions such as promoters by pyrosequencing of etiologically homogeneous sample pools after bisulfite treatment. We exemplify its use by the analysis of five genes (CDKN2A, GSTP1, MLH1, IGF2, and CTNNB1) involved in the pathogenesis of human hepatocellular carcinoma using pools stratified for different parameters of clinical importance. Results were confirmed by the individual analysis of the samples. The screening identified all genes displaying differential methylation successfully, and no false positives occurred. Quantitative comparison of the pools and the samples in the pool analyzed individually showed a deviation of ϳ1.5%, making the method ideally suited for the identification of diagnostic markers based on DNA methylation while saving precious DNA material. (J Mol Diagn 2007, 9:510 -520;

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“…The finding of elevated ErbB‐2 in the pathogenesis of hepatocellular carcinoma (HCC) differs among various studies. For example, elevated ErbB‐2 has been reported mostly in hyperplastic nodules, suggesting it is an early marker of hepatocarcinogenesis 9. Independent work showed elevated ErbB‐2 in 30–40% of HCCs analyzed 10, 11.…”

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confidence: 99%

Increased expression of ErbB‐2 in liver is associated with hepatitis B × antigen and shorter survival in patients with liver cancer

Liu

Ahiekpor

et al. 2009

Intl Journal of Cancer

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Hepatitis B 3 antigen, or HBxAg, contributes importantly to the pathogenesis of hepatocellular carcinoma (HCC). Given that HBxAg constitutively activates b-catenin and that upregulated ErbB-2 promotes b-catenin signaling in other tumor types, experiments were designed to ask whether HBxAg was associated with upregulated expression of ErbB-2. When HBxAg positive and negative HepG2 cells were subjected to proteomics analysis, ErbB-2 was shown to be upregulated in HepG2X but not control cells. ErbB-2 was also strongly upregulated in HB infected liver, and weakly in some HCC nodules, where it correlated with HBxAg expression. Among tumor bearing patients, strong ErbB-2 staining in the liver was associated with dysplasia, and a shorter survival after tumor diagnosis. This implies that elevated ErbB-2 is an early marker of HCC. Treatment of HepG2X cells with ErbB-2 specific siRNA not only reduced ErbB-2 expression, but also reduced the expression of b-catenin, suggesting that ErbB-2 contributed to the stabilization of b-catenin. ErbB-2 specific siRNA also partially blocked the ability of HBxAg to promote DNA synthesis and growth of HepG2 cells. These results suggest that ErbB-2/b-catenin up-regulation contributes importantly to the mechanism of HBxAg mediated hepatocellular growth. ' 2009 UICC

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Expression of c-erbB-2 and glutathione S-transferase-pi in hepatocellular carcinoma and its adjacent tissue

Cited by 20 publications

References 25 publications

Two‐dimensional differential gel electrophoresis/analysis of diethylnitrosamine induced rat hepatocellular carcinoma

Two‐dimensional differential gel electrophoresis/analysis of diethylnitrosamine induced rat hepatocellular carcinoma

Rapid Identification of Promoter Hypermethylation in Hepatocellular Carcinoma by Pyrosequencing of Etiologically Homogeneous Sample Pools

Increased expression of ErbB‐2 in liver is associated with hepatitis B × antigen and shorter survival in patients with liver cancer

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