title: Tumour response to gefitinib is associated with EGF- and gefitinib- but not radiation-modulated EGFR expression.
abstract: OBJECTIVE
  This study was conducted to explore the relationship between different treatment-modulated EGFR expression and gefitinib sensitivity.
  
  
  METHODS
  Gefitinib-sensitive (A431) and -resistant (A375, MALME-3M, and SK-MEL 5) tumour cell lines were treated with epidermal growth factor (EGF), gefitinib or radiation in vitro, and EGFR expression levels were measured by using ELISA.
  
  
  RESULTS
  EGF, and gefitinib treatment resulted in significantly higher levels of total and/or phosphorylated EGFR in sensitive than in resistant tumours and this was associated with gefitinib IC(50). In contrast, radiation-modulated EGFR expression, both total and phosphorylated, did not correlate with the efficacy of gefitinib. Stimulation of proliferation by EGF was significantly stronger in A431 than in the other three lines, indicating sensitive tumours were more EGFR-dependent than resistant tumours for cell proliferation.
  
  
  CONCLUSIONS
  These findings imply a potential role of EGF- and gefitinib-modulated EGFR expression in predicting gefitinib sensitivity.
authors.affiliation: ANSTO LifeSciences, Australian Nuclear Science and Technology Organisation, Lucas Heights, NSW 2234, Australia. hql@ansto.gov.au
authors.forename: Hui Qiang
authors.initials: HQ
authors.lastname: Lin
authors.forename: Andrew
authors.initials: A
authors.lastname: Katsifis
authors.forename: Haider
authors.initials: H
authors.lastname: Meriaty
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D048708:Cell Growth Processes / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000096:biosynthesis*; D000077156:Gefitinib; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D000077156:Gefitinib