title: [Mechanisms of EGF regulation of COX-2 through the STAT5 signaling pathway in human lung adenocarcinoma A549 cells].
abstract: BACKGROUND
  It has been proved that cyclooxygenase-2 (COX-2) is a key factor in lung cancer oncogenesis. COX-2 can be induced by a number of cytokines and growth factors and can be regulated by the JAK/STAT signaling pathway. Inhibiting the expression of COX-2 can prevent the development of lung cancer. The aim fo this study is to investigate whether the epidermal growth factor (EGF) can stimulate the signal transducers and activators of transcription 5 (STAT5) as well as to discover the effects of the STAT5 signaling pathway on the COX-2 in human lung adenocarcinoma A549 cells.
  
  
  METHODS
  The phenomenon of STAT5 activation stimulated by the EGF was assayed through immunofluorescence and Western blot. The adenovirus containing the wild-type (WT)-STAT5 (AdWT-STAT5) plasmid, dominant-negative (DN)-STAT5 (Ad-CMV5Stat5aΔ740) plasmid, and STAT5 siRNA were transfected into A549 cells. The latter two groups were stimulated using EGF. Reverse transcriptase polymerase chain reaction was used to detect the mRNA expression of COX-2.
  
  
  RESULTS
  STAT5 was not activated in A549 cells in vitro. EGF stimulation significantly increased the level of the p-STAT5 protein and induces the shuttling of p-STAT5 from the cytoplasm into the nucleus. STAT5 activation was crucial for the COX-2 expression induced by the EGF. STAT5 was required for COX-2 expression, but can mediated the effects of the COX-2 expression through pathways that were independent of transcriptional activation.
  
  
  CONCLUSIONS
  COX-2 expression is dependent on STAT5 phosphorylation. A second pathway does not require STAT5 phosphorylation.
authors.affiliation: Department of Thoracic Surgery, the Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Shouqiang
authors.initials: S
authors.lastname: Cao
authors.forename: Guibin
authors.initials: G
authors.lastname: Zhao
authors.forename: Qing
authors.initials: Q
authors.lastname: Dong
authors.forename: Jingquan
authors.initials: J
authors.lastname: Han
authors.forename: Yanzhong
authors.initials: Y
authors.lastname: Xin
authors.forename: Yubo
authors.initials: Y
authors.lastname: Yan
authors.forename: Jiyao
authors.initials: J
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Cui
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D010766:Phosphorylation / Q000187:drug effects; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D050799:STAT5 Transcription Factor; D004815:Epidermal Growth Factor; D051546:Cyclooxygenase 2