DNA integration sites and hepatocellular carcinoma
dc.contributor.author | Gumucio, Jorge J. | en_US |
dc.contributor.author | Daugherty, Daryl | en_US |
dc.contributor.author | Daugherty, Daryl | en_US |
dc.date.accessioned | 2006-04-28T16:53:39Z | |
dc.date.available | 2006-04-28T16:53:39Z | |
dc.date.issued | 1991-02 | en_US |
dc.identifier.citation | Gumucio, Jorge J.; Daugherty, Daryl; Daugherty, Daryl (1991)."DNA integration sites and hepatocellular carcinoma." Hepatology 13(2): 380-382. <http://hdl.handle.net/2027.42/38347> | en_US |
dc.identifier.issn | 0270-9139 | en_US |
dc.identifier.issn | 1527-3350 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/38347 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=1995445&dopt=citation | en_US |
dc.description.abstract | This study is part of an ongoing analysis of woodchuck hepatitis virus integration sites in the host genome of hepatocellular carcinomas. The study of woodchuck hepatitis virus-DNA integration sites may shed light on the oncogenic mechanisms involved in cellular transformation and tumor formation. Viral integration enhancing cellular proto-oncogene expression is one such mechanism and has been well documented for oncogenic retroviruses such as mouse mammary tumor virus and interleukin-1. By cloning a woodchuck hepatitis virus integration site from a woodchuck hepatocellular carcinoma the authors were able to identify a new member of the myc gene family, N- myc -2. Examination of 30 additional woodchuck hepatomas revealed viral integration commonly occurred near N- myc loci with an additional five woodchuck hepatitis virus integrants near the N- myc -2 gene and one viral integrant near N- myc -1. Three of these N- myc -2 viral integrations were further evaluated and found to be localized within 200 bp of the translation stop codon. This 3′ noncoding region has recently been identified as a common site of murine leukemia virus integration in virally induced T-cell lymphomas and results in increased expression of the N- myc gene. Similar mechanisms can be proposed for hepatocellular carcinoma formation. Woodchuck hepatitis virus integration near cell-growth related protooncogenes, such as N- myc , can juxtapose viral enhancer elements and growth-regulatory genes. Virally induced overexpression of proto-oncogene messenger RNA could result from enhanced transcription or increased messenger RNA stability. To search for such effects the authors analyzed N- myc -2 RNA levels in 30 woodchuck hepatitis virus-related hepatomas. Increased levels of N- myc -2 RNA were found in 18 of 30 tumors, whereas nontumorous portions of the same livers had no detectable N- myc -2 RNA. Taken together these findings suggest that woodchuck hepatitis virus integration can result in altered N- myc -2 gene expression in a significant proportion of woodchuck hepatocellular carcinomas. The deregulation of N- myc gene expression could result in cellular transformation and ultimately tumor formation. Such examples of hepadnavirus-specific oncogenic mechanisms lend credence to theories of hepatitis B virus-induced tumorigenesis and provide models to design molecular investigations of human hepatocellular carcinoma formation. | en_US |
dc.format.extent | 404165 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | |
dc.publisher | W.B. Saunders | en_US |
dc.publisher | Wiley Periodiocals, Inc. | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.subject.other | Hepatology | en_US |
dc.title | DNA integration sites and hepatocellular carcinoma | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Internal Medicine and Specialties | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Internal Medicine, Division of Gastroenterology, Room 111D, VA Medical Center/University of Michigan Ann Arbor, Michigan 48105 | en_US |
dc.contributor.affiliationum | Department of Internal Medicine, Division of Gastroenterology, Room 111D, VA Medical Center/University of Michigan Ann Arbor, Michigan 48105 | en_US |
dc.contributor.affiliationum | Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor, Michigan 48109–0682 | en_US |
dc.identifier.pmid | 1995445 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/38347/1/1840130229_ftp.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1002/hep.1840130229 | en_US |
dc.identifier.source | Hepatology | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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