title: Regulatory mechanisms of betacellulin in CXCL8 production from lung cancer cells.
abstract: BACKGROUND
  Betacellulin (BTC), a member of the epidermal growth factor (EGF) family, binds and activates ErbB1 and ErbB4 homodimers. BTC was expressed in tumors and involved in tumor growth progression. CXCL8 (interleukin-8) was involved in tumor cell proliferation via the transactivation of the epidermal growth factor receptor (EGFR).
  
  
  METHODS
  The present study was designed to investigate the possible interrelation between BTC and CXCL8 in human lung cancer cells (A549) and demonstrated the mechanisms of intracellular signals in the regulation of both functions. Bio-behaviors of A549 were assessed using Cell-IQ Alive Image Monitoring System.
  
  
  RESULTS
  We found that BTC significantly increased the production of CXCL8 through the activation of the EGFR-PI3K/Akt-Erk signal pathway. BTC induced the resistance of human lung cancer cells to TNF-α/CHX-induced apoptosis. Treatments with PI3K inhibitors, Erk1/2 inhibitor, or Erlotinib significantly inhibited BTC-induced CXCL8 production and cell proliferation and movement.
  
  
  CONCLUSIONS
  Our data indicated that CXCL8 production from lung cancer cells could be initiated by an autocrine mechanism or external sources of BTC through the EGFR-PI3K-Akt-Erk pathway to the formation of inflammatory microenvironment. BTC may act as a potential target to monitor and improve the development of lung cancer inflammation.
authors.forename: Lin
authors.initials: L
authors.lastname: Shi
authors.forename: Lingyan
authors.initials: L
authors.lastname: Wang
authors.forename: Beibei
authors.initials: B
authors.lastname: Wang
authors.forename: Sanda Maria
authors.initials: SM
authors.lastname: Cretoiu
authors.affiliation: Department of Pulmonary Medicine, The First affiliated Hospital, Wenzhou Medical University, Wenzhou, China. wang.qun@zs-hospital.sh.cn.
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Wang
authors.forename: Chengshui
authors.initials: C
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D066259:Betacellulin; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D000069347:Erlotinib Hydrochloride; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000378:metabolism*; D016209:Interleukin-8 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008175:Lung Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C587851:BTC protein, human; D066259:Betacellulin; C508606:CXCL8 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D008070:Lipopolysaccharides; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D014409:Tumor Necrosis Factor-alpha; D003513:Cycloheximide; D000069347:Erlotinib Hydrochloride; D019869:Phosphatidylinositol 3-Kinases; D020794:Receptor Protein-Tyrosine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases