|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
44
|
|
pubmed:dateCreated |
2000-10-26
|
|
pubmed:abstractText |
Deregulation of E2F transcriptional control has been implicated in oncogenic transformation. Consistent with this idea, we recently demonstrated that during hepatocarcinogenesis in c-myc/TGFalpha double transgenic mice, there is increased expression of E2F-1 and E2F-2, as well as induction of putative E2F target genes. Therefore, we generated transgenic mice expressing E2F-1 under the control of the albumin enhancer/promoter to test the hypothesis that E2F family members may contribute to liver tumor development. Overexpression of E2F-1 resulted in mild but persistent increases in cell proliferation and death during postnatal liver growth, and no increases in hepatic regenerative growth in response to partial hepatectomy. Nevertheless, from 2 months postnatally E2F-1 transgenic mice exhibited prominent hepatic histological abnormalities including preneoplastic foci adjacent to portal tracts and pericentral large cell dysplasia. From 6 to 8 months onward, there was an abrupt increase in the number of neoplastic nodules ('adenomas') with 100% incidence by 10 months. Some adenomas showed evidence of malignant transformation, and two of six mice killed at 12 months showed trabecular hepatocellular carcinoma. Endogenous c-myc was up-regulated in the early stages of E2F-1 hepatocarcinogenesis, whereas p53 was overexpressed in the tumors, suggesting that both E2F-1-mediated proliferation and apoptosis are operative but at different stages of hepatocarcinogenesis. In conclusion, E2F-1 overexpression in the liver causes dysplasia and tumors and suggests a cooperation between E2F-1 and c-myc oncogenes during liver oncogenesis.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Albumins,
http://linkedlifedata.com/resource/pubmed/chemical/Arid4a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/E2F Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/E2F1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/E2F1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/E2F2 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/E2F2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/E2f1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-myc,
http://linkedlifedata.com/resource/pubmed/chemical/Retinoblastoma-Binding Protein 1,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor DP1,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Oct
|
|
pubmed:issn |
0950-9232
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
19
|
|
pubmed:volume |
19
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
5054-62
|
|
pubmed:dateRevised |
2009-11-19
|
|
pubmed:meshHeading |
pubmed-meshheading:11042693-Albumins,
pubmed-meshheading:11042693-Animals,
pubmed-meshheading:11042693-Apoptosis,
pubmed-meshheading:11042693-Carrier Proteins,
pubmed-meshheading:11042693-Cell Cycle Proteins,
pubmed-meshheading:11042693-Cell Division,
pubmed-meshheading:11042693-Cell Transformation, Neoplastic,
pubmed-meshheading:11042693-Crosses, Genetic,
pubmed-meshheading:11042693-DNA-Binding Proteins,
pubmed-meshheading:11042693-E2F Transcription Factors,
pubmed-meshheading:11042693-E2F1 Transcription Factor,
pubmed-meshheading:11042693-E2F2 Transcription Factor,
pubmed-meshheading:11042693-Enhancer Elements, Genetic,
pubmed-meshheading:11042693-Female,
pubmed-meshheading:11042693-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:11042693-Genes, myc,
pubmed-meshheading:11042693-Hepatocytes,
pubmed-meshheading:11042693-Humans,
pubmed-meshheading:11042693-Liver,
pubmed-meshheading:11042693-Liver Neoplasms, Experimental,
pubmed-meshheading:11042693-Liver Regeneration,
pubmed-meshheading:11042693-Male,
pubmed-meshheading:11042693-Mice,
pubmed-meshheading:11042693-Mice, Inbred C57BL,
pubmed-meshheading:11042693-Mice, Inbred CBA,
pubmed-meshheading:11042693-Mice, Transgenic,
pubmed-meshheading:11042693-Precancerous Conditions,
pubmed-meshheading:11042693-Promoter Regions, Genetic,
pubmed-meshheading:11042693-Proto-Oncogene Proteins c-myc,
pubmed-meshheading:11042693-Retinoblastoma-Binding Protein 1,
pubmed-meshheading:11042693-Transcription Factor DP1,
pubmed-meshheading:11042693-Transcription Factors,
pubmed-meshheading:11042693-Tumor Suppressor Protein p53
|
|
pubmed:year |
2000
|
|
pubmed:articleTitle |
Dual functions of E2F-1 in a transgenic mouse model of liver carcinogenesis.
|
|
pubmed:affiliation |
Laboratory of Experimental Carcinogenesis, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, MD 20892, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
