Gene Set: WU_HBX_TARGETS_3_DN

Standard name WU_HBX_TARGETS_3_DN
Systematic name M3518
Brief description Genes down-regulated by expression of HBV X protein (HBVgp3) [GeneID=944566] both in SK-Hep-1 cells (hepatocellular carcinoma) and normal primary hepatocytes.
Full description or 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.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 11439330   Authors: Wu CG,Salvay DM,Forgues M,Valerie K,Farnsworth J,Markin RS,Wang XW
Exact source Table 1: Down-regulated
Related gene sets (show 5 additional gene sets from the source publication)

(show 10 gene sets from the same authors)
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Organism Homo sapiens
Contributed by John Newman (University of Washington)
Source platform HUMAN_GENE_SYMBOL
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Compendia expression profiles Human tissue compendium (Novartis)
NCI-60 cell lines (National Cancer Institute)
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Version history 3.0: Renamed from HBX_HEP_DN

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