Hepatitis B virus in hepatocarcinogenesis

Feitelson, Mark A.

doi:10.1002/(sici)1097-4652(199911)181:2<188::aid-jcp2>3.0.co;2-7

Cited by 100 publications

(44 citation statements)

References 191 publications

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“…HBx is a multi-functional protein (Brechot et al, 2000;Feitelson, 1999;Kew, 1997;Murakami, 1999;Yeh, 2000). However, most of the studies that involve the examination of HBx-mediated functions utilize tumor cell lines or ®broblasts.…”

Section: Discussionmentioning

confidence: 99%

“…The hepatitis B virus (HBV) has been clearly recognized as an etiological factor for hepatocellular carcinoma (HCC) (reviewed in Beasley, 1988;Bradley, 1999;Butel, 2000;Feitelson, 1999;Murakami, 1999;Robinson et al, 1999). Overwhelming evidence indicates a direct link between chronic infection with HBV and the development of HCC (Bova et al, 1991;Brechot et al, 1998;Harris and Sun, 1984).…”

Section: Introductionmentioning

confidence: 99%

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Distinctive gene expression profiles associated with Hepatitis B virus x protein

Salvay

Forgues

et al. 2001

Oncogene

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Distinctive gene expression profiles associated with Hepatitis B virus x protein

Salvay

Forgues

et al. 2001

Oncogene

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“…It is a trans-activating protein that stimulates HBV gene expression and replication, and also alters host gene expression important to the pathogenesis of chronic liver disease and the development of HCC associated with HBV [Feitelson, 1999].…”

Section: Hbx Regulation Of Ca IX Expression In Human Hepatocellular Cmentioning

confidence: 99%

Role of the HBx oncoprotein in carbonic anhydrase 9 induction

Holotnakova¹,

Tylková²,

Takáčová³

et al. 2009

Journal of Medical Virology

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International audienceCarbonic anhydrase 9 (CA9), as one of the most hypoxia-responsive genes, has been associated almost exclusively with hypoxic tumours. Its principal role is in pH regulation which helps tumour cells overcome intracellular acidosis and survive extended periods of time with low oxygen. Hypoxia-inducible factor 1 (HIF-1) is the main transcriptional activator of CA9. Hepatitis B virus X protein (HBx) has been shown to increase the transcriptional activity of HIF-1. HBx is often expressed from the gene integrated in the hepatocytes infected persistently and contributes significantly to alterations in host gene expression that can lead to the development of hepatocellular carcinoma (HCC) associated with HBV. The aim of this study was to determine the effect of HBx on expression of CA9. Transient transfection of HBx led to an increase in the expression of CA9 as assessed by RT-PCR and Western blotting. HBx was able to increase CA9 promoter activity significantly in several cell lines. The effect was mediated via HIF-1 and a functional HRE element located –10/–3 bp upstream of the CA9 transcription initiation site. These data suggest that CA9 may be involved in the development of HCC by contributing to the survival of hepatocytes infected with HBV in liver tissue with fibrosis

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“…Risk factors for HCC include viral hepatitis B and viral hepatitis C (HCV) infection that activate JAK/ STAT signaling, induce overexpression of insulinlike growth factor-II in 16-40% of HCCs (Breuhahn et al, 2006), and disrupt p53, p55 sen and p21 WAF1/CIP1/SDI1 (Ueda et al, 1995;Feitelson, 1999;Huo et al, 2001). Activation of the Wnt signaling pathway with b-catenin mutations is observed in 17-40% of HCCs and axin-2 inactivation in 3-10% of cases (Taniguchi et al, 2002;Ishizaki et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Disruption of transforming growth factor-β signaling through β-spectrin ELF leads to hepatocellular cancer through cyclin D1 activation

et al. 2007

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Transforming growth factor-b (TGF-b) signaling members, TGF-b receptor type II (TBRII), Smad2, Smad4 and Smad adaptor, embryonic liver fodrin (ELF), are prominent tumor suppressors in gastrointestinal cancers. Here, we show that 40% of elf þ /À mice spontaneously develop hepatocellular cancer (HCC) with markedly increased cyclin D1, cyclin-dependent kinase 4 (Cdk4), c-Myc and MDM2 expression. Reduced ELF but not TBRII, or Smad4 was observed in 8 of 9 human HCCs (Po0.017). ELF and TBRII are also markedly decreased in human HCC cell lines SNU-398 and SNU-475. Restoration of ELF and TBRII in SNU-398 cells markedly decreases cyclin D1 as well as hyperphosphorylated-retinoblastoma (hyperphosphorylated-pRb). Thus, we show that TGF-b signaling and Smad adaptor ELF suppress human hepatocarcinogenesis, potentially through cyclin D1 deregulation. Loss of ELF could serve as a primary event in progression toward a fully transformed phenotype and could hold promise for new therapeutic approaches in human HCCs.

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Hepatitis B virus in hepatocarcinogenesis

Cited by 100 publications

References 191 publications

Distinctive gene expression profiles associated with Hepatitis B virus x protein

Distinctive gene expression profiles associated with Hepatitis B virus x protein

Role of the HBx oncoprotein in carbonic anhydrase 9 induction

Disruption of transforming growth factor-β signaling through β-spectrin ELF leads to hepatocellular cancer through cyclin D1 activation

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