Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Woodchuck hepatitis virus (WHV) is a small, partially double-stranded DNA virus. Like the related human hepatitis B virus (HBV), WHV induces acute and chronic hepatitis and hepatocellular carcinoma (HCC) in its natural host. WHV DNA integration into c-myc and N-myc, resulting in deregulated expression of these genes, has been described previously in woodchuck HCC. We have analysed a woodchuck liver tumour in which WHV DNA was integrated in the c-myc gene. The virus insertion provoked multiple alterations in one c-myc allele, probably involving secondary deletions and mutations. Integrated viral DNA, including promotor and enhancer sequences, acted as an insertional mutagen, leading to enhanced expression of heterogenous c-myc transcripts ranging from 7.2 to 14 kb in size, strikingly longer than normal 2.3-kb c-myc RNA. These results provide an additional example in which the oncogenic activation of a myc gene by cis-acting effect of WHV insertion may play a critical role in virus-induced woodchuck HCC.
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PMID:Multiple rearrangements and activated expression of c-myc induced by woodchuck hepatitis virus integration in a primary liver tumour. 131 4

The expression of nine oncogenes (c-myc, N-myc, N-ras, H-ras, k-ras, abl, fos, src, and raf) and two tumor suppressor genes (p53 and RB) were studied by northern blot hybridization in six human hepatocellular carcinoma or hepatoblastoma cell lines (PLC/PRF/5, Hep3B, Hep G2, 2.2.15, HLE, and HLF) and in a human embryonic lung fibroblast cell line (WI-38) to look for differences that might be associated with the presence (PLC/PRF/5, Hep3B, and 2.2.15) or absence (Hep G2, HLE, and HLF) of integrated hepatitis B virus (HBV) DNA. The levels of expression of the oncogenes and tumor suppressor genes were unrelated to the presence or absence of integrated HBV-DNA. Furthermore, the intensity of expression of these oncogenes was no greater in the 2.2.15 cell line (consisting of Hep G2 cells transfected with hepatitis B virus) than in untransfected Hep G2 cells.
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PMID:Expression of oncogenes and tumor suppressor genes in human hepatocellular carcinoma and hepatoblastoma cell lines. 133 79

Hepatitis B virus is a major etiologic agent in the development of human hepatocellular carcinoma, but the precise role of the virus in the tumorigenic process is still unclear. Recent studies of naturally occurring animal models, such as woodchucks and squirrels infected with hepatitis B-like viruses (hepadnaviruses) have revealed different oncogenic strategies and outlined the predominant role of myc genes in rodent hepatomas. Higher oncogenicity of woodchuck hepatitis virus has been correlated with a direct contribution of the virus as an insertional mutagen of myc genes: c-myc, N-myc and predominantly the woodchuck N-myc retroposon. In contrast, rare viral integration events but frequent amplifications of c-myc characterize ground squirrel hepatitis virus-induced tumors, indicating that hepadnaviruses may contribute in malignant transformation through different, direct or indirect ways.
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PMID:Mammalian hepatitis B viruses and primary liver cancer. 133 94

Chronic infections with hepatitis B virus (HBV) of humans and animal hepadnavirus infections in their natural hosts are strongly associated with primary hepatocellular carcinoma (HCC). Although viral integrations are found in cells of many HCC, no general viral-specific hepatocarcinogenic mechanism for hepadnaviruses has been identified. In approximately one half of HCC in woodchuck hepatitis virus (WHV) infected woodchucks, viral integrations near the c-myc or N-myc genes have been reported which result in enhanced expression of the respective gene. Such host gene-specific insertional mutagenesis has not been found in HCC of other hepadnavirus infected hosts. Thus in humans, ground squirrels and ducks hepadnaviral integrations appear to be at different host chromosomal DNA sites in each HCC and few integrations have been found within or near any cellular gene. Other possible hepadnavirus-specific carcinogenic mechanisms that are being investigated include transactivation of cellular gene expression by an hepadnavirus gene product (e.g. the X-gene), and mutation of host genes by unknown hepadnavirus-specific mechanisms. It should be noted, however, that chronic hepadnavirus infection is associated with chronic necroinflammatory liver disease with hepatocellular necrosis and regeneration (sometimes leading to cirrhosis in humans), a pathological process that is common to numerous other risk factors for HCC. This suggests the possibility that this pathological process is hepatocarcinogenic irrespective of the inciting agent and the role of hepadnavirus infection is no different from that of other risk factors in causing chronic necroinflammatory liver disease.
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PMID:The role of hepatitis B virus in the development of primary hepatocellular carcinoma: Part I. 133 78

To study the oncogenesis of human esophageal carcinoma, the presence of DNA sequences homologous to several DNA tumor viruses and the expression of oncogenes and growth factor genes were examined in two esophageal carcinoma cell lines of Chinese origin, CE48T/VGH and CE81T/VGH. Southern blot analyses failed to detect sequences homologous to hepatitis B virus (HBV), Epstein-Barr virus (EBV), herpes simplex virus type 2 (HSV-2), cytomegalovirus (CMV) or human papilloma virus (HPV) genomes. Northern blot analyses revealed that c-myc, c-src, c-H-ras, c-abl, c-sis, and p53 genes were expressed. In addition, transcripts of transforming growth factor alpha (TGF alpha), TGF beta, and platelet derived growth factor A (PDGF A) genes were detected. These studies suggest that DNA tumor viruses may not be involved in the carcinogenesis of esophageal carcinoma. However, cooperation among different oncogenes and the production of growth factors may play an important role in that carcinogenesis.
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PMID:Absence of genomes of DNA tumor viruses and expression of oncogenes and growth factors in two esophageal carcinoma cell lines of Chinese origin. 147 73

Persistent infection with hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma (HCC) in humans. HCC has also been observed in animals chronically infected with two other hepadnaviruses: ground squirrel hepatitis virus (GSHV) and woodchuck hepatitis virus (WHV). A distinctive feature of WHV is the early onset of woodchuck tumors, which may be correlated with a direct role of the virus as an insertional mutagen of myc genes: c-myc, N-myc, and predominantly the woodchuck N-myc2 retroposon. In the present study, we searched for integrated GSHV DNA and genetic alterations of myc genes in ground squirrel HCCs. Viral integration into host DNA was detected in only 3/14 squirrel tumors and did not result in insertional activation of myc genes, despite the presence of a squirrel locus homologous to the woodchuck N-myc2 gene. This suggests that GSHV may differ from WHV in its reduced ability to induce mutagenic integration events. However, the high frequency of c-myc amplification (6/14) observed in ground squirrel HCCs indicates that myc genes might be preferential effectors in the tumorigenic processes associated with rodent hepadnaviruses, a feature not reported so far in HBV-induced carcinogenesis. Together with previous observations, our results suggest that hepadnaviruses, despite close genetic and biological properties, may use different pathways in the genesis of liver cancer.
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PMID:Frequent amplification of c-myc in ground squirrel liver tumors associated with past or ongoing infection with a hepadnavirus. 157 Mar 7

The products of the human hepatitis B virus (HBV) and woodchuck hepatitis B virus X genes (pXs) transactivate homologous and heterologous genes including the HBV-X and core promoters, the human immunodeficiency viruses 1 (HIV-1) and 2 (HIV-2) long terminal repeats and the beta interferon regulatory sequences. We report here that pX is also able to influence the expression of both extrachromosomal transfected c-myc regulatory sequences and endogenous c-myc gene. pX acts by increasing transcription of the c-myc gene and do not affect c-myc mRNAs stability. The presence of the first AUG of the X-ORFs is indeed necessary for the production of an active pX. The very carboxyterminus of the pX protein is dispensable for this transactivating activity and at least one domain important for its action is located between aminoacids 103 and 117.
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PMID:Full-length and truncated versions of the hepatitis B virus (HBV) X protein (pX) transactivate the cmyc protooncogene at the transcriptional level. 164 50

Hepatocellular carcinomas in woodchuck were characterized for woodchuck hepatitis virus integration near c-myc oncogene. In one tumor, viral integration resulted in overexpression of a c-myc viral cotranscript. In a second tumor, viral insertion, 600 bp upstream of c-myc exon 1, was associated with increased levels of normal c-myc mRNA. These results demonstrate that integration of woodchuck hepatitis virus near a proto-oncogene can contribute to the genesis of liver tumors. From a comparison of a single hepatitis B virus (HBV) integration site in a human hepatoma with the corresponding unoccupied site have shown HBV DNA insertion in a putative cellular exon. This exon presented striking similarity to the DNA-binding domain of the thyroid/steroid hormones receptors. The corresponding cDNA has been isolated (hap gene) a shown to encode the retinoic acid receptor. It is most probable that consequent to HBV insertion, has became inappropriately expressed as an altered chimaeric gene retinoic acid receptor, thus contributing to the cell transformation. As for woodchuck these results strongly support the possibility that HBV may play a direct role in liver carcinogenesis by insertional mutagenesis.
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PMID:[Hepatitis B virus and hepatocellular carcinoma]. 165 Jun 25

Several epidemiological studies have demonstrated a link between chronic B virus infection and primary hepatocellular carcinoma (PHC). HBV DNA sequence integrations into the host cell genome have often been observed in hepatocarcinoma tissues. However, since only in a few cases of PHC the target of HBV-DNA insertion has been identified, alternative mechanisms for HBV-induced hepatocyte transformation have been investigated. Like many other DNA viruses, the hepatitis B virus bears a transactivational potential. Both full length and truncated versions of HBV X protein are able to influence the expression of cellular nuclear protooncogenes c-fos and c-myc. A second transcriptional activator is encoded by the PreS/S region of HBV, but its activity on viral and cellular genes become evident only after dislocations from its downstream sequences. Thus, HBV is able to influence infected cell growth and differentiation using both native proteins, newly generated truncated proteins and virus-cell fusion polypeptides.
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PMID:Hepatitis B virus and hepatocellular carcinoma: a possible role for the viral transactivators. 166 93

The in vitro effect of sodium butyrate (SB) on human hepatoma cell lines PLC/PRF/5, HCC-M and HCC-T was investigated. SB was added at the non-toxic but cytostatic concentration of 1 mM. In all these cell lines, SB reduced cell proliferation and changed the morphology of the cells into a fibroblast-like shape. In PLC/PRF/5, alpha-fetoprotein production and c-myc expression were inhibited. In contrast, gene expression of albumin, one of the normal liver-cell products, and that of integrated hepatitis B virus genome, was increased. In HCC-M and HCC-T, c-myc expression, which was enhanced in the naive state, was reduced. In HCC-M, fos expression was inhibited but the expression of N- and K-ras genes did not change. SB seemed to induce normal or mature properties of hepatocytes in human hepatoma cell lines.
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PMID:Differentiating effect of sodium butyrate on human hepatoma cell lines PLC/PRF/5, HCC-M and HCC-T. 170 67


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