title: Regulation of epidermal growth factor receptor in human colon cancer cell lines by interferon alpha.
abstract: OBJECTIVE
  The biology of growth factor receptor expression has implications for receptor specific cancer therapy. In this study, we examined: (a) regulation of epidermal growth factor receptor (EGFR) expression in a panel of 10 human colon cancer cell lines using interferon alpha (IFN-alpha); (b) ability of IFN-alpha to inhibit cell proliferation; and (c) sensitivity of IFN-alpha pretreated cells to EGF.
  
  
  METHODS
  Cell proliferation was measured both by crystal violet colorimetric and clonogenic assays. Cell surface, intracellular, and/or total cell protein expression of EGFR was assessed by indirect immunofluorescence flow cytometry and/or fluorescein isothiocyanate (FITC)-EGF binding and internalisation flow cytometric assay.
  
  
  RESULTS
  IFN-alpha treatment upregulated expression of cell surface EGFR in seven of 10 colon cancer cell lines within 16 hours, reaching a peak within 48-96 hours; this was accompanied by transient elevation of intracellular EGFR and marked growth inhibition. IFN-alpha treated cancer cells were still sensitive to EGF proliferative stimulation.
  
  
  CONCLUSIONS
  Our results indicate that cytostatic concentrations of IFN-alpha can enhance cell surface and intracellular EGFR expression in a proportion of human colon cancer cells. The antiproliferative action of IFN-alpha could not block the signal transduction of the EGF-EGFR pathway. This may have clinical implications for improving treatment based on targeting of EGFR.
authors.affiliation: Department of Surgery, Prince of Wales Hospital, University of New South Wales, Sydney, Australia.
authors.forename: J-L
authors.initials: JL
authors.lastname: Yang
authors.forename: X-J
authors.initials: XJ
authors.lastname: Qu
authors.forename: P J
authors.initials: PJ
authors.lastname: Russell
authors.forename: D
authors.initials: D
authors.lastname: Goldstein
mesh_terms: D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016898:Interferon-alpha; D009363:Neoplasm Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors