The involvement of the hepatitis B virus in the pathogenesis of hepatocellular carcinoma was initially suggested on the basis of epidemiological studies. In recent years several kinds of experimental evidence have supported this hypothesis; however, the role played by hepatitis B virus in hepatocarcinogenesis still needs to be elucidated. Several groups of researchers are presently involved in establishing whether hepatitis B virus makes a specific genetic contribution to carcinogenesis or predisposes to neoplastic transformation by causing chronic inflammation and cell regeneration. A comprehensive examination of the data available in the literature suggests that the two hypotheses may not be mutually exclusive.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] ABSTRACT: AbstrAct Hepadnaviruses employ an unusual strategy for the production of enormous number of virions during replication which makes rapid and substantial genetic sequence changes and alterations. The pathogenesis and clearance of hepatitis B virus (HBV) infection are engaged by the selection and expression of viral mutants dur-ing virus-host interactions. Mutations in regulatory regions such as the basal core promoter (BCP) which is thought to be related to lower production of hepatitis B "e" antigen (HBeAg) directly affects the clinical presentation of liver disease. However, the molecular structure of these mutations in chronic carriers has not been adequately evaluated. In this review we evaluate the molecular aspect and pathologic basis of basal core promoter mutations.
Middle East journal of digestive diseases 02/2011; 3(1).
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