Mechanisms of HBV-related hepatocarcinogenesis

Oncogenesis and Molecular Virology Unit, Institut Pasteur, Inserm U579, 28 rue du Dr Roux, Paris cedex 15, France.
Journal of Hepatology (Impact Factor: 10.4). 04/2010; 52(4):594-604. DOI: 10.1016/j.jhep.2009.10.033
Source: PubMed

ABSTRACT The hepatitis B virus (HBV) is a small enveloped DNA virus, which primarily infects hepatocytes and causes acute and persistent liver disease. Epidemiological studies have provided overwhelming evidence for a causal role of chronic HBV infection in the development of hepatocellular carcinoma, but the molecular mechanisms underlying virally-induced tumourigenesis remain largely debated. In the absence of a dominant oncogene encoded by the HBV genome, indirect roles have been proposed, including insertional activation of cellular cancer-related genes by HBV DNA integration, induction of genetic instability by viral integration or by the regulatory protein HBx, and long-term effects of viral proteins in enhancing immune-mediated liver disease. Recent genetic studies indicate that HBV-related tumours display a distinctive profile with a high rate of chromosomal alterations and low frequency of beta-catenin mutations. This review will discuss the evidence implicating chronic HBV infection as a causal risk factor of primary liver cancer. It will also discuss the molecular mechanisms that are critical for the tumourigenic process due to long lasting infection with HBV.

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Available from: Marie-Annick Buendia, Jul 29, 2015
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    • "In addition, a conjunction of risk factors is frequent in clinical practice, and the specific impact of each factor in hepatocarcinogenesis is difficult to evaluate. The most clear-cut direct carcinogenic role is that of chronic hepatitis B infection, that can lead to HCC outside of the background of cirrhosis [11]. It includes well known viral integration into the tumour genome, but also the potential oncogenic role of viral protein. "
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    ABSTRACT: Hepatocellular carcinoma is related to various etiologies including hepatitis B, hepatitis C, high alcohol intake, aflatoxin B1 and metabolic syndrom. Most of the time HCC developped on cirrhosis. Consequently, the mechanims of carcinogenesis of these different risk factors are difficult to separate from the events leading to cirrhosis. In contrast, aflatoxin B1 and hepatitis B have a clear direct oncogenic role through point mutations in the TP53 tumor supressor gene and insertionnal mutagenesis respectively. Finally, next-generation sequencing and transcriptome analysis will refine our knowledge of the relationship between etiology and the genetic events that draw the mutationnal landscape of hepatocellular carcinoma.
    Baillière&#x027 s Best Practice and Research in Clinical Gastroenterology 10/2014; 28(5). DOI:10.1016/j.bpg.2014.08.006 · 3.28 Impact Factor
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    • "As shown in Table 1 and discussed in the aforementioned reviews, all the three signal pathways known to respond differently to drug treatments as described in the previous section are regulated by HBx (Ng and Lee 2011; Arzumanyan et al. 2012). Hence, HBx is sometimes considered to be a viral oncoprotein (Koike 2009; Neuveut et al. 2010) and could be the chief regulator of the differential gene expression between HepG2 and Hep3B because it regulates the majority of those genes listed in Table 1. "
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    ABSTRACT: As cellular models for in vitro liver cancer and toxicity studies, HepG2 and Hep3B are the two most frequently used liver cancer cell lines. Because of their similarities they are often treated as the same in experimental studies. However, there are many differences that have been largely over-sighted or ignored between them. In this review, we summarize the differences between HepG2 and Hep3B cell lines that can be found in the literature based on PubMed search. We particularly focus on the differential gene expression, differential drug responses (chemosensitivity, cell cycle and growth inhibition, and gene induction), signaling pathways associated with these differences, as well as the factors in governing these differences between HepG2 and Hep3B cell lines. Based on our analyses of the available data, we suggest that neither HBx nor p53 may be the crucial factor to determine the differences between HepG2 and Hep3B cell lines although HBx regulates the expression of the majority of genes that are differentially expressed between HepG2 and Hep3B. Instead, the different maturation stages in cancer development of the original specimen between HepG2 and Hep3B may be responsible for the differences between them. This review provides insight into the molecular mechanisms underlying the differences between HepG2 and Hep3B and help investigators especially the beginners in the areas of liver cancer research and drug metabolism to fully understand, and thus better use and interpret the data from these two cell lines in their studies.
    Cytotechnology 07/2014; 67(1). DOI:10.1007/s10616-014-9761-9 · 1.45 Impact Factor
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    • "The core (C) ORF encodes both hepatitis B core antigen (HBcAg), which is a structural nucleocapsid core protein, and hepatitis B e antigen (HBeAg), which is a soluble nucleocapsid protein (Fig. 1C). The X ORF encodes hepatitis B x protein (HBx), which plays roles in signal transduction, transcriptional activation , DNA repair, and inhibition of protein degradation [Neuveut et al., 2010]. "
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    ABSTRACT: Hepatitis B virus (HBV) poses a threat to global public health mainly because of complications of HBV-related chronic liver disease. HBV exhibits a narrow host range, replicating primarily in hepatocytes by a still poorly understood mechanism. For the generation of progeny virions, HBV depends on interactions with specific host factors through its life cycle. Revealing and characterizing these interactions are keys to identifying novel antiviral targets, and to developing specific treatment strategies for HBV patients. In this review, recent insights into the HBV-host interactions, especially on virus entry, intracellular trafficking, genome transcription and replication, budding and release, and even cellular restriction factors were reviewed. J. Med. Virol. © 2014 Wiley Periodicals, Inc.
    Journal of Medical Virology 06/2014; 86(6):925-32. DOI:10.1002/jmv.23916 · 2.22 Impact Factor
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