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Pegged for destruction: Beta‐catenin as a novel target of pegylated interferon.
Author(s) -
Thompson Michael David,
Micsenyi Amanda,
Monga Satdarshan PS
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a71-d
Subject(s) - wnt signaling pathway , hepatocellular carcinoma , pegylated interferon , western blot , cell culture , interferon , hep g2 , cancer research , medicine , gene knockdown , hepatitis c virus , virology , chemistry , signal transduction , virus , biology , gene , biochemistry , ribavirin , genetics
Pegylated‐Interferon (IFN) or Pegasys © is one of the few known treatments for patients suffering from chronic Hepatitis C virus (HCV) infection. Interestingly, one observed consequence of such treatment is a decrease in occurrence of hepatocellular carcinoma (HCC) in HCV patients. Overall, HCC remains the most common forms of liver cancer, accounting for 90% of all primary liver tumors. Mutations leading to Wnt/β‐catenin activation contribute in the development of a significant subset of HCC. Furthermore, activation of this pathway has been noted in many cases of HCV infection. We explored the possibility that IFN's anti‐HCC activity is through inhibitory actions on the Wnt/β‐catenin signaling. We treated 2 human hepatoma cell lines (HepG2 & Hep3B) to test for IFN at 100U/ml. Hep G2 and Hep3B primary cell cultures were treated with pegylated IFN at a dose of 100U/ml every 48 hours for 3, 6, 8, and 12 doses. Western blot analysis and RNA measurement was carried out on protein samples. Transcriptional activity was measured in HepG2 cells after 3 doses via the TOPFLASH luciferase reporter assay. Treatment with Pegasys © decreased active‐β‐catenin levels when compared to control cultures. Likewise, β‐catenin RNA levels & TOPFLASH luciferase activity were significantly decreased following treatment. This was associated with hypodense and sparse cultures. These results suggest an inhibitory effect of Pegasys © on the Wnt signaling pathway and may be a mechanism of delayed HCC in treated HCV patients.