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.

Comments

Reproduced with permission of BioMed Central. Infectious Agents and Cancer.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

Peer Reviewed

1

Open Access

1

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