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Published on: September 25, 2019
PTEN modulates hepatitis B virus-X protein induced survival signaling in Chang liver cells
Sukmi Kang-Park1, Jee H Im, Je H Lee
1Liver Cell Signal Transduction Lab., Molecular Cancer Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejon 305-606, Republic of Korea.
Abstract:
PTEN gene, a novel tumor suppressor is frequently mutated or deleted in several malignancies including human hepatocellular carcinoma (HCC). We report previously that human hepatitis B virus-X (HBx) protein achieves protection from apoptotic cell death through-PI3K-Akt-Bad signaling that is p53-independent in liver cells (JBC; 276, 16969 (2000)). In this report, we demonstrated the PTEN effect on HBx induced anti-apoptotic signaling in Chang liver cells (CHL). Expression of PTEN in CHL cells downregulate HBx induced PI3K, Akt activities, Akt, Bad phosphorylations, decreased caspase 3 activity and protection from DNA fragmentations. PTEN suppression of CHL cell growth at G1 phase (JBC;278,4057(2003)) in cell cycle analysis, which is overcome by HBx activated Akt/PKB further confirmed that same PI3K/Akt pathway is involved in cell survival and apoptosis by HBx and PTEN. PTEN suppression of HBx-mediated cell survival through PI3K pathway is specific, since PTEN does not suppress the effect of HBx on the protection from Fas-mediated apoptosis. Taken together, these findings demonstrate that PTEN potently modulate HBx-mediated signaling and is a viable target in therapeutic approaches to inhibit the formation of HCC caused by HBV infections.
Insights
PTEN suppresses hepatitis B virus-X (HBx) protein-induced anti-apoptotic signaling in liver cells. This finding suggests PTEN as a therapeutic target to inhibit hepatitis B virus-associated hepatocellular carcinoma (HCC).
Area of Science:
- Molecular Biology
- Oncology
- Virology
Background:
- The PTEN gene, a tumor suppressor, is often altered in cancers like hepatocellular carcinoma (HCC).
- Hepatitis B virus-X (HBx) protein protects liver cells from apoptosis via the PI3K-Akt-Bad pathway.
- The interplay between PTEN and HBx in HCC pathogenesis requires further elucidation.
Purpose of the Study:
- To investigate the effect of PTEN on HBx-induced anti-apoptotic signaling in Chang liver cells (CHL).
- To determine the role of the PI3K/Akt pathway in mediating cell survival and apoptosis influenced by HBx and PTEN.
Main Methods:
- PTEN expression was analyzed in CHL cells.
- PI3K and Akt activities, phosphorylation of Akt and Bad, caspase 3 activity, and DNA fragmentation were measured.
- Cell cycle analysis was performed to assess the impact on cell growth.
- The specificity of PTEN's effect was tested using Fas-mediated apoptosis.
Main Results:
- PTEN expression downregulated HBx-induced PI3K and Akt activities, as well as Akt and Bad phosphorylation.
- PTEN reduced caspase 3 activity and DNA fragmentation, indicating decreased apoptosis.
- PTEN inhibited CHL cell growth at the G1 phase, an effect overcome by HBx-activated Akt/PKB.
- PTEN's suppression of HBx-mediated cell survival was specific to the PI3K pathway and did not affect Fas-mediated apoptosis.
Conclusions:
- PTEN potently modulates HBx-mediated signaling pathways involved in cell survival and apoptosis.
- PTEN represents a potential therapeutic target for inhibiting HCC development in HBV infections.
