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Distinctive gene expression profiles associated with Hepatitis B virus x protein

Oncogene volume 20, pages 3674–3682 (2001)Cite this article

Abstract

Hepatitis B virus (HBV) is a major risk factor for the development of hepatocellular carcinoma (HCC). HBV encodes the potentially oncogenic HBx protein, which mainly functions as a transcriptional co-activator involving in multiple gene deregulations. However, mechanisms underlying HBx-mediated oncogenicity remain unclear. To determine the role(s) of HBx in the early genesis of HCC, we utilized the NCI Oncochip microarray that contains 2208 human cDNA clones to examine the gene expression profiles in either freshly isolated normal primary adult human hepatocytes (Hhep) or an HCC cell line (SK-Hep-1) ecotopically expressing HBx via an adenoviral system. The gene expression profiles also were determined in liver samples from HBV-infected chronic active hepatitis patients when compared with normal liver samples. The microarray results were validated through Northern blot analysis of the expression of selected genes. Using reciprocally labeling hybridizations, scatterplot analysis of gene expression ratios in human primary hepatocytes expressing HBx demonstrates that microarrays are highly reproducible. The comparison of gene expression profiles between HBx-expressing primary hepatocytes and HBV-infected liver samples shows a consistent alteration of many cellular genes including a subset of oncogenes (such as c-myc and c-myb) and tumor suppressor genes (such as APC, p53, WAF1 and WT1). Furthermore, clustering algorithm analysis showed distinctive gene expression profiles in Hhep and SK-Hep-1 cells. Our findings are consistent with the hypothesis that the deregulation of cellular genes by oncogenic HBx may be an early event that favors hepatocyte proliferation during liver carcinogenesis.

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Acknowledgements

We are grateful to Dr Lance Miller for technical assistance with the microarray studies. We also thank Drs Curtis C Harris and Ana I Robles for critically reading the manuscript, and Dorothea Dudek for editorial assistance. This work was supported, in part, by the Intramural Research Program of the National Cancer Institute. DM Salvay was supported by the Biomedical Engineering Summer Internship Program funded by the Whitaker Foundation of National Institutes of Health.

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Authors and Affiliations

  1. Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD 20892-4255, Maryland, USA

    Chuan-Ging Wu, David M Salvay, Marshonna Forgues & Xin Wei Wang

  2. Department of Radiation Oncology, Medical College of Virginia, Virginia Commonwealth University, 23298-0058, Richmond, Virginia, VA VA, USA

    Kristoffer Valerie & Julie Farnsworth

  3. Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198-3135, Nebraska, USA

    Rodney S Markin

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Wu, CG., Salvay, D., Forgues, M. et al. Distinctive gene expression profiles associated with Hepatitis B virus x protein. Oncogene 20, 3674–3682 (2001). https://doi.org/10.1038/sj.onc.1204481

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