PTEN modulates hepatitis B virus-X protein induced survival signaling in Chang liver cells
| Autor: | Sukmi Kang-Park, Je H. Lee, Jee H. Im, Young Ik Lee |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Cancer Research
Hepatitis B virus Cell Survival viruses Caspase 3 Apoptosis DNA Fragmentation Transfection Cell Line Phosphatidylinositol 3-Kinases Virology PTEN Humans Viral Regulatory and Accessory Proteins Phosphorylation Protein kinase B PI3K/AKT/mTOR pathway biology Cell growth Cell Cycle PTEN Phosphohydrolase Cell cycle digestive system diseases HBx Infectious Diseases Cancer research biology.protein Hepatocytes Trans-Activators bcl-Associated Death Protein Proto-Oncogene Proteins c-akt |
| Zdroj: | Virus research. 122(1-2) |
| ISSN: | 0168-1702 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect