Document Type
Journal Article
Publication Date
1-2015
Journal
Infectious Agents and Cancer
Volume
10
Inclusive Pages
24
DOI
10.1186/s13027-015-0018-9
Abstract
BACKGROUND AND AIMS: 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.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
APA Citation
Wang, Z., Wu, N., Tesfaye, A., Feinstone, S., & Kumar, A. (2015). HCV infection-associated hepatocellular carcinoma in humanized mice. Infectious Agents and Cancer, 10, 24.
Peer Reviewed
1
Open Access
1
Comments
Reproduced with permission of BioMed Central. Infectious Agents and Cancer.