PTEN modulates hepatitis B virus-X protein induced survival signaling in Chang liver cells.
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.
Kang-Park
Sukmi
S
Liver Cell Signal Transduction Lab., Molecular Cancer Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejon 305-606, Republic of Korea.
Im
Jee H
JH
Lee
Je H
JH
Lee
Young I
YI
D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival; D053938:DNA Fragmentation; D006515:Hepatitis B virus; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism* / Q000821:virology; D006801:Humans; D051059:PTEN Phosphohydrolase / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015534:Trans-Activators; D014162:Transfection; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism*; D051025:bcl-Associated Death Protein / Q000378:metabolism
C494819:BAD protein, human; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; D051025:bcl-Associated Death Protein; C057628:hepatitis B virus X protein; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D053148:Caspase 3