Conditional hepatocarcinogenesis in mice expressing SV 40 early sequences.
We closely mimicked the in vivo setting in which sporadic hepatocarcinoma occurs by establishing a transgenic mouse model carrying regulatable SV40 early sequences under the control of the regulatory sequences of the human antithrombin III gene that confer hepatic expression. In this system, floxed dormant oncogenic sequences became functional after excision due to adenoviral expression of Cre recombinase or the stable transgenic expression in liver of a tamoxifen-inducible Cre. Hepatic oncogene expression was switched on by both methods, leading to the development of hepatocellular carcinoma. This model could be useful for investigating the key steps of the preneoplastic process, to identify suitable targets for the testing of new therapies.
Lou
Dan-Qing
DQ
Département GDPM, Institut Cochin, INSERM U-567, CNRS UMR 8104, Université Paris 5, 24 rue du Faubourg Saint-Jacques, 75014 Paris, France.
Molina
Thierry
T
Bennoun
Myriam
M
Porteu
Arlette
A
Briand
Pascale
P
Joulin
Virginie
V
Vasseur-Cognet
Mireille
M
Cavard
Catherine
C
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D000990:Antithrombin III / Q000235:genetics / Q000502:physiology; D006528:Carcinoma, Hepatocellular / Q000503:physiopathology / Q000662:veterinary / Q000821:virology*; D004195:Disease Models, Animal; D004790:Enzyme Induction; D020224:Expressed Sequence Tags; D015972:Gene Expression Regulation, Neoplastic; D019426:Integrases / Q000096:biosynthesis; D008113:Liver Neoplasms / Q000503:physiopathology / Q000662:veterinary / Q000821:virology*; D051379:Mice; D008822:Mice, Transgenic; D013539:Simian virus 40 / Q000235:genetics*; D013629:Tamoxifen / Q000494:pharmacology; D014764:Viral Proteins / Q000096:biosynthesis
D018931:Antineoplastic Agents, Hormonal; D014764:Viral Proteins; D013629:Tamoxifen; D000990:Antithrombin III; C045073:Cre recombinase; D019426:Integrases