title: Human leptin protein induces proliferation of A549 cells via inhibition of PKR-like ER kinase and activating transcription factor-6 mediated apoptosis.
abstract: OBJECTIVE
  To investigate the anti-apoptotic mechanism of leptin in non-small cell lung cancer.
  
  
  METHODS
  The influences of leptin on apoptosis were investigated, analyzing the mechanism that triggers growth of A549 cells. The effects of leptin on cell proliferation were examined by XTT analysis. Leptin, C/EBP homologous protein (CHOP), phosphorylated-PKR-like ER kinase (p-Perk), inositol requiring proteins-1, spliced X-box transcription factor-1 (XBP1), cleaved activating transcription factor-6 (ATF6), eukaryotic translation initiation factor-2α, caspase-12 and CHOP protein were detected in four groups by western blot, and endoplasmic reticulum (ER) stress related mRNA were detected by reverse transcription PCR.
  
  
  RESULTS
  The expression of leptin in A549 and leptin transfected cells inhibited cisplatin activated ER stress-associated mRNA transcription and protein activation. Two ER stress unfolded protein response pathways, PERK and ATF6, were involved, and XBP1 and tumor necrosis factor receptor-associated factor 2 (TRAF2) were increased significantly when treated with cisplatin in A549-siRNA against leptin cells. Furthermore, CHOP expression was inhibited upon leptin expression in A549, LPT-PeP and LPT-EX cells.
  
  
  CONCLUSIONS
  Leptin serves as an important factor that promotes the growth of A549 cells through blocking ER stress-mediated pathways. This blocking is triggered by p-Perk and ATF6 via inhibition of CHOP expression.
authors.affiliation: Department of Thoracic Surgery, General Hospital of Zaozhuang Mining Group, Qi lian shan Road 12, Shandong, Zaozhuang 277000, China. laiqunzz@yeah.net.
authors.forename: Qun
authors.initials: Q
authors.lastname: Lai
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
mesh_terms: D051702:Activating Transcription Factor 6 / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D020738:Leptin / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019892:eIF-2 Kinase / Q000378:metabolism*
chemical_list: D051702:Activating Transcription Factor 6; D020738:Leptin; D019892:eIF-2 Kinase
keywords: Apoptosis; ER stress; TRAF2; XPB1; cell growth; leptin