Functional role of phosphatidylinositol 3-kinase/Akt pathway on cell growth and lytic cycle of Epstein-Barr virus in the Burkitt's lymphoma cell line, P3HR-1.
The phosphatidylinositol 3-kinase (PI3-K)/Akt pathway is involved in various malignancies, but the role of PI3-K/Akt pathway in Epstein-Barr virus (EBV) infected Burkitt's lymphoma (BL) cells remains unclear. To elucidate therapeutic targets for BL, this study investigates the effect of PI3-K/Akt pathway in: EBV-positive BL cell lines Raji, P3HR-1, Akata and Daudi; and EBV-negative BL cell lines Ramos and BJAB. Results of analyses indicate that Akt was constitutively phosphorylated in BJAB, P3HR-1, Akata, and Daudi but not in Ramos and Raji cells. We characterized Akt phosphorylation on cell growth and EBV lytic cycle in P3HR-1 cells, which were phosphorylated most intensively. The Akt was equally phosphorylated in cells cultured with and without fetal bovine serum for a few days. Akt phosphorylation and cell growth were inhibited by PI3-K specific inhibitor LY294002 in a dose-dependent manner. LY294002 markedly down regulated expression of EBV lytic gene BRLF1 protein Rta, BMRF1 protein EA-D, but not BZLF1 protein ZEBRA. The inhibitor reduced viral capsid antigen (VCA) positive cells. Down regulation of Rta by LY294002 occurred at the transcriptional level. These results demonstrate that PI3-K/Akt pathway is activated constitutively in P3HR-1 cells; it promotes cell growth and the lytic cycle cascade downstream of ZEBRA.
Mori
Takako
T
Division of Biosignaling, Department of Biomedical Sciences, School of Life Science, Faculty of Medicine, Tottori University, 86 Nishi-cho, 683-8503, Yonago, Japan.
Sairenji
Takeshi
T
D001402:B-Lymphocytes / Q000821:virology; D002051:Burkitt Lymphoma / Q000473:pathology; D045744:Cell Line, Tumor; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004854:Herpesvirus 4, Human / Q000187:drug effects / Q000472:pathogenicity* / Q000502:physiology*; D006801:Humans; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D014775:Virus Activation; D014779:Virus Replication
D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt