Abstract

Hepatitis B virus (HBV) encoded x antigen (HBxAg) is a /raws-activating protein that contributes to the development of hepatocellular carcinoma (HCC) by the up- or down-regulated expression of selected hepatocellular genes. To identify some of these genes, HBxAg or vector were introduced into the human hepatoblastoma cell line, HepG2. Differentially expressed genes were identified by microarray analysis and by PowerBlot (SDS/PAGE followed by western blotting). Both assays showed decreased E-cadherin and increased expression of p-catenin and several p-catenin target genes in HBxAg [+] compared to [-] cells. In the livers of HBV carriers, there was an inverse relationship between HBxAg staining and E-cadherin and co- staining between HBxAg and p-catenin, suggesting that HBxAg contributes to hepatocellular transformation by altering the P-catenin signaling pathway. Hence, the objective of this work is to elucidate the mechanisms whereby HBxAg stabilizes p-catenin and thereby stimulates signaling, and to determine the contribution of these mechanisms to HBxAg mediated transformation. Accordingly, experiments will test the hypothesis that the accumulation/activation of p-catenin in HBxAg positive cells results from HBxAg /r

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA104025-04
Application #
7339815
Study Section
Cancer Etiology Study Section (CE)
Program Officer
Read-Connole, Elizabeth Lee
Project Start
2006-02-06
Project End
2011-01-31
Budget Start
2009-02-01
Budget End
2010-01-31
Support Year
4
Fiscal Year
2009
Total Cost
$256,657
Indirect Cost

  Institution

Name
Temple University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
057123192
City
Philadelphia
State
PA
Country
United States
Zip Code
19122

  Publications

Feitelson, Mark A; Bonamassa, Barbara; Arzumanyan, Alla (2014) The roles of hepatitis B virus-encoded X protein in virus replication and the pathogenesis of chronic liver disease. Expert Opin Ther Targets 18:293-306
Mesri, Enrique A; Feitelson, Mark A; Munger, Karl (2014) Human viral oncogenesis: a cancer hallmarks analysis. Cell Host Microbe 15:266-82
Arzumanyan, Alla; Reis, Helena M G P V; Feitelson, Mark A (2013) Pathogenic mechanisms in HBV- and HCV-associated hepatocellular carcinoma. Nat Rev Cancer 13:123-35
Arzumanyan, A; Friedman, T; Kotei, E et al. (2012) Epigenetic repression of E-cadherin expression by hepatitis B virus x antigen in liver cancer. Oncogene 31:563-72
Yuan, Ke; Lian, Zhaorui; Sun, Bill et al. (2012) Role of miR-148a in hepatitis B associated hepatocellular carcinoma. PLoS One 7:e35331
Schinazi, Raymond F; Bassit, Leda; Clayton, Marcia M et al. (2012) Evaluation of single and combination therapies with tenofovir disoproxil fumarate and emtricitabine in vitro and in a robust mouse model supporting high levels of hepatitis B virus replication. Antimicrob Agents Chemother 56:6186-91
Arzumanyan, Alla; Friedman, Tiffany; Ng, Irene O L et al. (2011) Does the hepatitis B antigen HBx promote the appearance of liver cancer stem cells? Cancer Res 71:3701-8
Feitelson, Mark A; Reis, Helena M G P V; Tufan, N Lale et al. (2009) Putative roles of hepatitis B x antigen in the pathogenesis of chronic liver disease. Cancer Lett 286:69-79
Liu, Jie; Ahiekpor, Angela; Li, Li et al. (2009) Increased expression of ErbB-2 in liver is associated with hepatitis B x antigen and shorter survival in patients with liver cancer. Int J Cancer 125:1894-901
Cao, Wenjun; Sun, Bill; Feitelson, Mark A et al. (2009) Hepatitis C virus targets over-expression of arginase I in hepatocarcinogenesis. Int J Cancer 124:2886-92

Showing the most recent 10 out of 18 publications