Development of a transgenic mouse model of hepatocellular carcinoma with a liver fibrosis background

BMC Gastroenterology
Sook In ChungSimon Weonsang Ro

Abstract

Liver fibrosis and its end-stage disease, cirrhosis, are major risk factors for hepatocellular carcinoma (HCC) and present in 80 to 90 % of patients with HCC. Current genetically engineered mouse models for HCC, however, generally do not feature liver fibrosis, which is a critical discrepancy between human HCC and murine models thereof. In this study, we developed a simple transgenic mouse model of HCC within the context of a fibrotic liver. Employing hydrodynamic transfection (HT), coupled with the Sleeping Beauty (SB) transposon system, liver was stably transfected with transposons expressing cMyc and a short hairpin RNA down-regulating p53 (shp53). A chronic liver injury model, induced by hepatotoxic carbon tetrachloride (CCl4), was applied to the transgenic mice, allowing cells expressing cMyc plus shp53 to become malignant in the background of liver fibrosis. Livers harvested about 3 months after HT had excessive collagen deposition and activated hepatic stellate cells surrounding the tumors. Hepatocarcinogenesis was significantly accelerated in the fibrotic livers compared to those of the control, significantly decreasing the life span of the mice. The tumor incidence and average number of tumors per mouse were significan...Continue Reading

References

Jan 1, 1991·Advances in Experimental Medicine and Biology·I G SipesD L Earnest
Mar 11, 1999·The New England Journal of Medicine·N Ince, J R Wands
Nov 13, 2001·Oncogene·A TannapfelC Wittekind
Oct 3, 2002·Nature Reviews. Cancer·Stella PelengarisGerard Evan
Oct 24, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Manal M HassanYehuda Z Patt
Apr 24, 2003·Critical Reviews in Toxicology·Lutz W D WeberAndreas Stampfl
Oct 28, 2004·Gastroenterology·Giovanna FattovichFrancesco Donato
Nov 27, 2004·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Isao SakaidaKiwamu Okita
Jun 14, 2005·Gut·M E Guicciardi, G J Gores
Nov 16, 2005·Proceedings of the National Academy of Sciences of the United States of America·Corey M CarlsonDavid A Largaespada
Aug 25, 2006·Nature Reviews. Cancer·Paraskevi A Farazi, Ronald A DePinho
Jun 16, 2007·Gastroenterology·Hashem B El-Serag, K Lenhard Rudolph
Dec 28, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Christof SchlaegerBernhard Radlwimmer
Mar 4, 2008·Journal of Hepatology·Philippa NewellJosep M Llovet
May 13, 2008·Gastroenterology·Scott L Friedman
Jan 17, 2009·Cancer Research·Stephen M WiesnerJohn R Ohlfest
Aug 8, 2009·International Journal of Experimental Pathology·Femke HeindryckxHans Van Vlierberghe
Mar 9, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Mustafa S AschaNizar N Zein
Nov 16, 2010·Annual Review of Pathology·Virginia Hernandez-Gea, Scott L Friedman
Feb 26, 2011·Annals of the Rheumatic Diseases·Sergei I Grivennikov, Michael Karin
Oct 14, 2011·The New England Journal of Medicine·Hashem B El-Serag
Nov 1, 2011·Immunity·Ali KuraishySergei I Grivennikov
Apr 3, 2012·Cell·Chi V Dang
Feb 1, 2014·The American Journal of Pathology·Xin Chen, Diego F Calvisi
Feb 26, 2014·Nature Reviews. Immunology·Antonella PellicoroJonathan A Fallowfield

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Citations

Mar 21, 2018·International Journal of Molecular Sciences·Jelena KrsticAndreas Prokesch
Dec 22, 2019·Cancers·Kyungjoo ChoSeung Up Kim
Feb 1, 2019·International Journal of Molecular Sciences·Hyuk MoonSimon Weonsang Ro
Nov 17, 2019·Cancers·Enya LiDa-Liang Ou
Jan 15, 2019·Molecular Therapy. Nucleic Acids·Elisa CallegariMassimo Negrini
Aug 8, 2021·Cancers·Alexandru BlidiselOctavian Marius Cretu

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Methods Mentioned

BETA
transfection
transgenic
PCR

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