Distinctive gene expression profiles associated with Hepatitis B virus x protein

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

doi:10.1038/sj.onc.1204481

Cited by 85 publications

(59 citation statements)

References 54 publications

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“…Previous research suggests that the possible molecular mechanism of HBx oncogenecity is a feature of its ability to misappropriate gene transcription, cell cycling, cell responses to genotoxic stress, protein degradation and signal transduction, ultimately leading to a disrupted balance between cell growth and apoptosis, resulting in carcinogenesis. [2][3][4][5][6][7] Despite the great progress achieved in studying HBx oncogenic mechanisms, the accurate molecular changes accompanying the expression of HBx remains unresolved. In previous study, we have generated an HBx transgenic mouse strain by introducing the HBx gene into the p21 locus.…”

Section: Abbreviationsmentioning

confidence: 99%

Expression profiling reveals dysregulation of cellular cytoskeletal genes in HBx–induced hepatocarcinogenesis

Sun¹,

Wang²,

Zhang³

et al. 2007

Cancer Biology & Therapy

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The molecular mechanisms underlying hepatitis B virus encoded HBx proteinmediated tumorigenesis are not fully understood. In order to gain a better view of the effects of HBx on transcriptional regulation and hepatocarcinogenesis, the expression profiles of liver and tumor tissues from 6-and 18-month-old p21-HBx transgenic and control mice were monitored using oligo microarrays. Data analysis demonstrated that 42 genes were deregulated in both 6-and 18-month-old HBx transgenic mouse tissues. Gene ontology assisted analysis classified these genes into functionally related clusters that encode proteins related to metabolism, signal transduction, transcription regulation and stress responses. Among them, cytoskeletal genes, including microtubule genes tubulinb2 (Tubb2), tubulinb3 (Tubb3) and tubulinb6 (Tubb6), intermediate filament genes periplakin, keratin 8 (K8) and keratin 18 (K18) and acting1 (Actg1), were closely clustered and upregulated in liver tissues. These results were validated by semi-quantitative RT-PCR in both mouse and human HCC tissues. The upregulation of K8 and K18 was only detected in p21-HBx but not p21-HBsAg liver tissues, suggesting that the global change in the expression of cellular cytoskeletal genes was correlated with the expression of HBx transgene. These findings propose for the first time that systemic dysregulation of cellular cytoskeletal genes is involved in HBx-induced hepatocarcinogenesis. AbbreviAtioNSHBV, hepatitis virus B; HCC, hepatocellular carcinoma; Hprt, hypoxanthine phosphoribosyltransferase; RT-PCR, reverse transcription polymerase chain reaction; APOBEC-1, apo-B mRNA-editing enzyme catalytic polypeptide 1; ALAS2, aminolevulinate synthase 2; HSP70, heat shock protein

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Section: Abbreviationsmentioning

confidence: 99%

Expression profiling reveals dysregulation of cellular cytoskeletal genes in HBx–induced hepatocarcinogenesis

Sun¹,

Wang²,

Zhang³

et al. 2007

Cancer Biology & Therapy

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“…[20][21][22][23] However, mRNA expression analysis is hampered, since in livers bearing hepatocellular carcinoma the non-neoplastic tissues already reveal distinct dysregulated sets of genes as also found in hepatocellular carcinoma. [24][25][26] We therefore focused on the comparison of hepatocellular carcinoma and hepatocellular adenoma, a rare tumour, almost never reported as becoming malignant.…”

Section: Scnn1amentioning

confidence: 99%

“…The results provided new information on classification, aetiology, survival prediction, and identification of signalling pathways that could serve as therapeutic targets. [1][2][3][4][5] Functional genomics integrating comparison with genetically modified mice as models for human hepatocellular carcinoma 6 as well as data from promoter regions, 7 expression of non-coding genes, that is, microRNA, 8 or array-based comparative genomic hybridisation (aCGH) 9 has further increased the reliability and significance of the biological and clinical conclusions drawn from gene expression profiles. This will be the basis for developing new targeted therapies, an urgent need to reduce the mortality from hepatocellular carcinoma, which represents the fourth most common malignant tumour with more than one million patients affected worldwide per year, and usually has a very poor prognosis.…”

mentioning

confidence: 99%

Gene expression profiling in hepatocellular carcinoma: upregulation of genes in amplified chromosome regions

et al. 2008

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“…The WNT/β-catenin pathways and MMT might be directly associated with hepatocarcinogenesis. 123 Other factors that could contribute to disease and are known to be elevated during cirrhosis are TGF-β, gelatinases, fibroblast-activating proteins, and members of the interferon response pathway. 123 Thus, several factors can lead to HCC -directly or indirectly and alone or in combination.…”

Section: Fibrogenesis and Chronic Hbv Infectionmentioning

confidence: 99%

Molecular Pathogenesis of Hepatitis-B-virus-associated Hepatocellular Carcinoma

Park¹,

Song²,

Chung³

2007

Gut Liver

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Hepatocellular carcinoma (HCC) is one of the most frequent and malignant diseases worldwide. Epidemiological studies have clearly demonstrated that chronic hepatitis B virus (HBV) infection is a major etiological factor in the development of HCC. The pathogenesis of HBV-associated HCC has been studied extensively, and the molecular changes associated with malignant transformation have been identified. The predominant carcinogenic mechanisms of HBV-associated HCC are chronic inflammation and the effects of cytokines in the development of fibrosis and liver cell proliferation. An important role is also played by the integration of HBV DNA into host cellular DNA, which disrupts or promotes the expression of cellular genes that are important in cell growth and differentiation. Especially, HBx protein is a transactivating protein that promotes cell growth, survival, and the development of HCC. Continued investigation of the mechanisms underlying hepatocarcinogenesis will refine our current understanding of the molecular and cellular basis for neoplastic transformation in the liver. Prevention of HBV infections and effective treatments for chronic hepatitis B are still needed for the global control of HBV-associated HCC. This review summarizes the current knowledge on the mechanisms involved in HBV-associated hepatocarcinogenesis. (Gut and Liver 2007;1: 101-117)

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Distinctive gene expression profiles associated with Hepatitis B virus x protein

Cited by 85 publications

References 54 publications

Expression profiling reveals dysregulation of cellular cytoskeletal genes in HBx–induced hepatocarcinogenesis

Expression profiling reveals dysregulation of cellular cytoskeletal genes in HBx–induced hepatocarcinogenesis

Gene expression profiling in hepatocellular carcinoma: upregulation of genes in amplified chromosome regions

Molecular Pathogenesis of Hepatitis-B-virus-associated Hepatocellular Carcinoma

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