title: EGFRvIII does not affect radiosensitivity with or without gefitinib treatment in glioblastoma cells.
abstract: BACKGROUND
  Glioblastomas (GBM) are often characterized by an elevated expression of the epidermal growth factor receptor variant III (EGFRvIII). We used GBM cell lines with native EGFRvIII expression to determine whether this EGFR variant affects radiosensitivity with or without EGFR targeting.
  
  
  METHODS
  Experiments were performed with GBM cell lines lacking (LN229, U87MG, U251, CAS-1) or endogenously expressing EGFRvIII (BS153, DKMG). The two latter cell lines were also used to establish sublines with a low (-) or a high proportion (+) of cells expressing EGFRvIII. EGFR signaling and the cell cycle were analyzed using Western blot and flow cytometry; cell survival was assessed by colony forming assay and double-strand break repair capacity by immunofluorescence.
  
  
  RESULTS
  DKMG and BS153 parental cells with heterogeneous EGFRvIII expression were clearly more radiosensitive compared to other GBM cell lines without EGFRvIII expression. However, no significant difference was observed in cell proliferation, clonogenicity or radiosensitivity between the EGFRvIII- and + sublines derived from DKMG and BS153 parental cells. Expression of EGFRvIII was associated with decreased DSB repair capacity for BS153 but not for DKMG cells. The effects of EGFR targeting by gefitinib alone or in combination with irradiation were also found not to depend on EGFRvIII expression. Gefitinib was only observed to influence the proliferation of EGFRvIII- BS153 cells.
  
  
  CONCLUSIONS
  The data indicate that EGFRvIII does not alter radiosensitivity with or without anti-EGFR treatment.
authors.affiliation: Department of Radiotherapy and Radio-Oncology, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Struve
authors.affiliation: Department of Radiotherapy and Radio-Oncology, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Riedel
authors.affiliation: Department of Neurosurgery, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Schulte
authors.affiliation: Department of Radiotherapy and Radio-Oncology, University Medical Center Hamburg Eppendorf, Hamburg, Germany.|Department of Otorhinolaryngology and Head and Neck Surgery, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Rieckmann
authors.affiliation: Department of Pathology, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
authors.forename: Tobias J
authors.initials: TJ
authors.lastname: Grob
authors.affiliation: Department of Human Genetics, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Gal
authors.affiliation: Department of Radiotherapy and Radio-Oncology, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Rothkamm
authors.affiliation: Department of Neurosurgery, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Lamszus
authors.affiliation: Department of Radiotherapy and Radio-Oncology, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
authors.forename: Cordula
authors.initials: C
authors.lastname: Petersen
authors.affiliation: Department of Radiotherapy and Radio-Oncology, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Dikomey
authors.affiliation: Department of Radiotherapy and Radio-Oncology, University Medical Center Hamburg Eppendorf, Hamburg, Germany.
authors.forename: Malte
authors.initials: M
authors.lastname: Kriegs
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002469:Cell Separation; D002470:Cell Survival; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D000077156:Gefitinib; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy*; D006801:Humans; D008856:Microscopy, Fluorescence; D011799:Quinazolines / Q000627:therapeutic use*; D011836:Radiation Tolerance; D015398:Signal Transduction; D014965:X-Rays
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; C410723:epidermal growth factor receptor VIII; D066246:ErbB Receptors; D000077156:Gefitinib
keywords: EGFRvIII; X-irradiation; gefitinib; glioblastoma; radiosensitivity