Distinctive gene expression profiles associated with hepatitis B virus x protein

Chuan Ging Wu, David M. Salvay, Marshonna Forgues, Kristoffer Valerie, Julie Farnsworth, Rodney S. Markin, Xin Wei Wang

Research output: Contribution to journalArticle

81 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3674-3682
Number of pages9
JournalOncogene
Volume20
Issue number28
DOIs
StatePublished - Jun 21 2001

Keywords

  • Chronic active hepatitis
  • Hepatitis B virus
  • Liver cancer
  • cDNA microarray

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Fingerprint Dive into the research topics of 'Distinctive gene expression profiles associated with hepatitis B virus x protein'. Together they form a unique fingerprint.

  • Cite this

    Wu, C. G., Salvay, D. M., Forgues, M., Valerie, K., Farnsworth, J., Markin, R. S., & Wang, X. W. (2001). Distinctive gene expression profiles associated with hepatitis B virus x protein. Oncogene, 20(28), 3674-3682. https://doi.org/10.1038/sj.onc.1204481