title: [Cross-talk between PI3K/Akt and MEK/ERK pathways regulates human hepatocellular carcinoma cell cycle progression under endoplasmic reticulum stress].
abstract: OBJECTIVE
  To investigate the cross-talk between the PI3K/Akt and MEK/ERK pathways and its role in cell cycle regulation under endoplasmic reticulum stress in human hepatocellular carcinoma cells.
  
  
  METHODS
  PI3K inhibitor LY294002 and MEK inhibitor U0126 were used to block the PI3K/Akt and MEK/ERK pathways respectively, and constitutively activated Akt mutant construct was used to activate the PI3K/Akt pathway. Western blot was used to study the potential cross-talk between the PI3K/Akt and MEK/ERK pathways under endoplasmic reticulum stress in human hepatocellular carcinoma cells. the role of the cross-talk between the PI3K/Akt and MEK/ERK pathways in cell cycle regulation was investigated by using propidium iodide staining.
  
  
  RESULTS
  LY294002 not only blocked Akt activation efficiently but also increased ERK phosphorylation markedly under endoplasmic reticulum stress in SMMC-7721 and Hep3B cells. Furthermore, myr-Akt inhibited endoplasmic reticulum stress-mediated ERK phosphorylation. In contrast, MEK inhibitor U0126 had no effect on endoplasmic reticulum stress-induced Akt activation. It is notable that both myr-Akt overexpression and MEK inhibitor U0126 inhibited endoplasmic reticulum stress-induced G0/G1 phase arrest in SMMC-7721 cells.
  
  
  CONCLUSIONS
  Endoplasmic reticulum stress-induced Akt activation is mediated through PI3K and the PI3K/Akt pathway inactivation is involved in increased ERK activity in human hepatocellular carcinoma cells. The cross-talk between the PI3K/Akt and MEK/ERK cascades plays an important role in endoplasmic reticulum stress-induced human hepatocellular carcinoma cell cycle arrest.
authors.affiliation: Department of Biochemistry, Luzhou Medical College, Luzhou Sichuan Province 646000, China.
authors.forename: Dong-mei
authors.initials: DM
authors.lastname: Yan
authors.forename: Rong-yang
authors.initials: RY
authors.lastname: Dai
authors.forename: Chun-yan
authors.initials: CY
authors.lastname: Duan
authors.forename: Shao-kun
authors.initials: SK
authors.lastname: Chen
authors.forename: You-ping
authors.initials: YP
authors.lastname: Liu
authors.forename: Chuan-ning
authors.initials: CN
authors.lastname: Chen
authors.forename: Hong
authors.initials: H
authors.lastname: Li
mesh_terms: D002070:Butadienes / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002867:Chromones / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D002070:Butadienes; D002867:Chromones; D009025:Morpholines; D009570:Nitriles; C113580:U 0126; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases