title: [The effects of ceruloplasmin in PI3K/PTEN cell signaling pathway change induced by silica].
abstract: OBJECTIVE
  To investigate the roles of ceruloplasmin (Cp) in PI3K/PTEN cell signaling pathway change in human embryonic lung fibroblasts (HELFs) induced by silica.
  
  
  METHODS
  HELFs transfected with pGenesil1.1 plasmid and pGenesil1.1 with PTEN shRNA (PT) plasmid were successfully established. 100 µg/ml silica and different concentrations of Cp (10, 20, 30 µg/ml) were used in this experiment and Cp were treated cells after exposed to silica for 1h. Three different cell lines (including HELFs, PT and cells were transfected with p85 dominant negative mutant plasmid (DN-p85)) were divided into control groups, silica groups and silica+different concentrations of Cp groups. MTT assay was used to detect the effects of Cp on silica-induced cell proliferation after inhibiting PTEN and p85. When suppressing the expression of PTEN and p85, western blot assay was performed to detect the levels of p85, p110, AKT308, AKT473 and ERK, JNK and their phosphorylated levels.
  
  
  RESULTS
  After inhibition of PTEN, the high levels of p85 induced by 100 µg/ml silica with 30 µg/ml Cp were markedly decreased (P<0.05). When suppressing p85, the increased cell proliferation was not observed. And the high levels of AKT308, AKT473, ERK and phosphorylated JNK and ERK stimulated by 100 µg/ml silica with 30 µg/ml Cp were decrease (P < 0.05).
  
  
  CONCLUSIONS
  Cp could further strengthened silica-induced cell proliferation by PI3K/AKT/MAPK cell signaling pathway, of which the level of p85 was regulated by PTEN.
authors.affiliation: Key Laboratory of Chemical Safety and Health, National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, China.
authors.forename: Xianan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Chemical Safety and Health, National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, China.
authors.forename: Yuegang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Chemical Safety and Health, National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Jia
authors.affiliation: Key Laboratory of Chemical Safety and Health, National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, China.
authors.forename: Bingci
authors.initials: B
authors.lastname: Liu
authors.affiliation: Key Laboratory of Chemical Safety and Health, National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, China. E-mail: yemeng1@chinacdc.cn.
authors.forename: Meng
authors.initials: M
authors.lastname: Ye
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002570:Ceruloplasmin / Q000494:pharmacology*; D058543:Class Ia Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D012822:Silicon Dioxide / Q000633:toxicity
chemical_list: D012822:Silicon Dioxide; D002570:Ceruloplasmin; D058543:Class Ia Phosphatidylinositol 3-Kinase; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human