Document Detail

Hepatocarcinogenesis in transgenic mice carrying albumin-promoted SV40 T antigen gene.
MedLine Citation:
PMID:  1684356     Owner:  NLM     Status:  MEDLINE    
We have developed transgenic mice that inherit albumin promoter-regulated simian virus 40 (SV40) large T antigen gene, expressed specifically in hepatocytes. These mice all develop multifocal hepatocellular carcinomas at around 5 months and die of liver insufficiency by 7 months. Sequential morphological observation of hepatocarcinogenesis revealed 5 distinct stages: (I) newborn to 2 weeks of age, neither recognizable histological changes nor cellular replication in spite of T antigen expression; (II) between 3 and 7 weeks, diffuse cytomegalic change of hepatocytes with numerous abnormal mitoses, usually resulting in cell death; (III) from 7 weeks onwards, quasi-regenerative small hepatocyte foci with a decreased tendency for cytomegaly in spite of T antigen expression, rapidly replacing the hepatic tissue; (IV) 11 weeks of age and thereafter, neoplastic foci and nodules with enzymatic alteration; (V) 20 weeks of age and thereafter, gross hepatocellular carcinomas with occasional pulmonary metastases. Considerable variation existed both in morphological and enzymatic features and T antigen expression among neoplastic lesions, including carcinomas. Thus, these transgenic mice clearly show a multistep process in hepatocarcinogenesis with remarkable synchrony and provide a promising model for analyzing the essential events of carcinogenesis at different stages.
O Hino; T Kitagawa; K Nomura; K Ohtake; L Cui; Y Furuta; S Aizawa
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Japanese journal of cancer research : Gann     Volume:  82     ISSN:  0910-5050     ISO Abbreviation:  Jpn. J. Cancer Res.     Publication Date:  1991 Nov 
Date Detail:
Created Date:  1992-01-24     Completed Date:  1992-01-24     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8509412     Medline TA:  Jpn J Cancer Res     Country:  JAPAN    
Other Details:
Languages:  eng     Pagination:  1226-33     Citation Subset:  IM    
Department of Pathology, Cancer Institute, Tokyo.
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MeSH Terms
Antigens, Polyomavirus Transforming / genetics*
Blotting, Northern
Crosses, Genetic
Glucose-6-Phosphatase / analysis
Liver / cytology,  microbiology,  pathology*
Liver Neoplasms, Experimental / genetics*,  microbiology,  pathology
Mice, Inbred Strains
Mice, Transgenic
Mitotic Index
Promoter Regions, Genetic*
Restriction Mapping
Serum Albumin / genetics*
Simian virus 40 / genetics*
Tumor Markers, Biological / analysis
gamma-Glutamyltransferase / analysis
Reg. No./Substance:
0/Antigens, Polyomavirus Transforming; 0/Serum Albumin; 0/Tumor Markers, Biological; EC; EC

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