title: Molecular profiling of EGFR family in chronic obstructive pulmonary disease: correlation with airway obstruction.
abstract: BACKGROUND
  Growth factors mediate various cellular responses to environmental stimuli. Specifically, exposure of lung epithelium to oxidative stress induced by cigarette smoke stimulates aberrant epidermal growth factor receptor (ERBB) family activation. This study's objective was to evaluate the expression of ERBB1-4 receptors in the lung tissue of smokers with or without chronic obstructive pulmonary disease (COPD).
  
  
  METHODS
  ERBBs expression was measured by microarray analysis in lung tissue samples from five patients with COPD and five non-COPD smokers, and by quantitative real-time PCR in additional 20 patients with COPD (GOLD stage II), 15 non-COPD smokers and 10 nonsmoker controls.
  
  
  RESULTS
  Microarray data analysis revealed that ERBB receptors expression was elevated in patients with COPD compared to non-COPD smokers, ranging from 1·62- to 2·45-fold, (P < 0·01). Real-time qPCR verified that patients with COPD had higher ERBB1-3 expression levels compared with non-COPD smokers (PERBB1  < 0·001; PERBB2  = 0·003; PERBB3  = 0·003) and nonsmokers (PERBB1  = 0·019; PERBB2  = 0·005; PERBB3  = 0·011). On the other hand, ERBB4 mRNA levels gradually increased from nonsmokers (0·74 ± 0·19) to non-COPD smokers (1·11 ± 0·05) to patients with COPD (1·57 ± 0·28) and were correlated with the degree of airflow obstruction (PFEV1  < 0·001).
  
  
  CONCLUSIONS
  These data suggest that ERBB1-3 overexpression is not related only to smoking exposure but probably to epithelial remodelling and mucociliary system distortion, characterizing COPD. Additionally, the inverse correlation of ERBB4 with FEV1 exhibits a possible link between ERBB4 and COPD severity.
authors.affiliation: Department of Thoracic Medicine, University Hospital of Heraklion, Crete, Greece; Laboratory of Molecular and Cellular Pulmonology, Medical School, University of Crete, Heraklion, Greece.
authors.forename: Aristotelis
authors.initials: A
authors.lastname: Anagnostis
authors.forename: Eirini
authors.initials: E
authors.lastname: Neofytou
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Soulitzis
authors.forename: Dimitris
authors.initials: D
authors.lastname: Kampas
authors.forename: Ioannis
authors.initials: I
authors.lastname: Drositis
authors.forename: Despina
authors.initials: D
authors.lastname: Dermitzaki
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Tzanakis
authors.forename: Sofia
authors.initials: S
authors.lastname: Schiza
authors.forename: Nikolaos M
authors.initials: NM
authors.lastname: Siafakas
authors.forename: Eleni G
authors.initials: EG
authors.lastname: Tzortzaki
mesh_terms: D000402:Airway Obstruction / Q000378:metabolism*; D018076:DNA, Complementary / Q000096:biosynthesis; D066246:ErbB Receptors / Q000378:metabolism*; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D008168:Lung / Q000378:metabolism; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012907:Smoking / Q000378:metabolism; D014797:Vital Capacity / Q000502:physiology
chemical_list: D018076:DNA, Complementary; D012313:RNA; D066246:ErbB Receptors
keywords: Chronic obstructive pulmonary disease; degree of airway obstruction; epidermal growth factor receptor; forced expiratory volume in first second; smoking