Open AccessHepatocarcinogenesis in Transgenic Mice Carrying Albumin‐promoted SV40 T Antigen Gene
Author(s) -
Hino Okio,
Kitagawa Tomoyuki,
Nomura Kimie,
Ohtake Keiko,
Cui Lixin,
Furuta Yasuhide,
Shinichi Shinichi
Publication year - 1991
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1991.tb01785.x
Subject(s) - biology , carcinogenesis , antigen , hepatocyte , genetically modified mouse , hepatocellular carcinoma , transgene , pathology , neoplastic transformation , immunohistochemistry , sv40 large t antigen , albumin , gene expression , cancer research , gene , immunology , transfection , endocrinology , medicine , biochemistry , in vitro
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.