title: Ionizing radiation affects epidermal growth factor receptor signalling and metalloproteinase secretion in glioma cells.
abstract: BACKGROUND
  The effect of different doses of X(-)rays on apoptosis, proliferation, epidermal growth factor receptor (EGFR) and matrix metalloproteinase (MMP-2) expression was investigated in a human glioblastoma cell line.
  
  
  METHODS
  The cell line LN18 was irradiated at room temperature with doses ranging from 0.5 to 15 Gy using 6 MV X(-)rays. Apoptosis was assessed using the annexin V binding assay, proliferation by the methyl tetrazolium (MTT) assay and MMP-2 secretion with zymography. The levels of phosphorylated (pEGFR) were estimated using a commercially available ELISA kit.
  
  
  RESULTS
  Cell proliferation decreased in a dose-dependent manner, while apoptosis was increased after radiation. Doses below 2 Gy did not affect proliferation or apoptosis. MMP-2 levels were increased 48 h after radiation in a dose-dependent manner. In contrast, EGFR signaling was significantly activated 15 min after radiation in a dose-dependent manner.
  
  
  CONCLUSIONS
  Ionizing radiation activates EGFR signalling and enhances MMP-2 secretion, suggesting that the molecular pathways involved may contribute to the invasiveness and malignant behaviour of glioma cells and help to explain the response of gliomas to ionizing radiation.
authors.affiliation: Department of Radiation Oncology, University of Patras Medical School, University Campus, 26504 Patras, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Martinou
authors.forename: Efstathia
authors.initials: E
authors.lastname: Giannopoulou
authors.forename: Georgia
authors.initials: G
authors.lastname: Malatara
authors.forename: Andreas A
authors.initials: AA
authors.lastname: Argyriou
authors.forename: Haralabos P
authors.initials: HP
authors.lastname: Kalofonos
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Kardamakis
mesh_terms: D017209:Apoptosis / Q000528:radiation effects*; D001932:Brain Neoplasms / Q000201:enzymology* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D005909:Glioblastoma / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D010766:Phosphorylation; D018000:Receptors, Peptide / Q000737:chemistry; D013778:Tetrazolium Salts / Q000737:chemistry; D013844:Thiazoles / Q000737:chemistry; D014965:X-Rays
chemical_list: D018000:Receptors, Peptide; D013778:Tetrazolium Salts; D013844:Thiazoles; C080707:annexin V receptor; D066246:ErbB Receptors; D020778:Matrix Metalloproteinase 2; C022616:thiazolyl blue