title: HCV infection-associated hepatocellular carcinoma in humanized mice.
abstract: OBJECTIVE
  Hepatitis C virus (HCV) infection is a major risk factor for chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC). Our aim is to explore molecular changes that underlie HCV infection-associated HCC in a humanized mouse model, in order to identify markers of HCC progression.
  
  
  METHODS
  Liver proteins from human hepatocyte-engrafted and HCV-infected MUP-uPA/SCID/Bg mice were compared with either uninfected controls or HCV-infected but HCC-negative mice by Western blotting. MicroRNA markers of HCC positive or uninfected mouse liver were analyzed by RT-PCR.
  
  
  RESULTS
  We describe the depletion of tumor suppressor proteins and induction of oncoproteins and oncogenic microRNAs (oncomiRs) in HCV-infection associated HCC. Similar depletion of PTEN protein in both HCC-positive and HCV-infected but HCC-negative liver suggests that PTEN depletion is an early, precancerous marker of HCC. By contrast, induction of oncoprotein cMyc, oncomiRs (miR21, miR221 and miR141) and inflammatory response proteins correspond to HCC progression.
  
  
  CONCLUSIONS
  While the loss of PTEN is important for the initiation of HCV infection-associated HCC, PTEN depletion by itself is insufficient for tumor progression. Liver tumor progression requires induction of oncoproteins and oncomiRs. Overall, human hepatocyte-engrafted (MUP-uPA/SCID/Bg) mice provide a suitable small animal model for studying the effects of oncogenic changes that promote HCV infection associated HCC.
authors.affiliation: Department of Biochemistry and Molecular Medicine, The George Washington University, Washington, DC 20037 USA.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Medicine, The George Washington University, Washington, DC 20037 USA.
authors.forename: Ningbin
authors.initials: N
authors.lastname: Wu
authors.affiliation: Division of Viral Products, Center for Biologics Evaluation and Research, FDA, Bethesda, MD 20892 USA.
authors.forename: Abeba
authors.initials: A
authors.lastname: Tesfaye
authors.affiliation: Department of Biochemistry and Molecular Medicine, The George Washington University, Washington, DC 20037 USA.|Division of Viral Products, Center for Biologics Evaluation and Research, FDA, Bethesda, MD 20892 USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Feinstone
authors.affiliation: Department of Biochemistry and Molecular Medicine, The George Washington University, Washington, DC 20037 USA.|Biochemistry and Molecular Medicine, The George Washington University, Ross Hall room 232, 2300 Eye Street, N.W., Washington, DC 20037 USA.
authors.forename: Ajit
authors.initials: A
authors.lastname: Kumar
keywords: HCV Infection-associated HCC