title: Targeting of EGFR and HER2 with therapeutic antibodies and siRNA: a comparative study in glioblastoma cells.
abstract: BACKGROUND
  The epidermal growth factor receptors, EGFR (HER1) and HER2, have proven prognostic relevance in a variety of human malignancies and both are functionally involved in the molecular pathogenesis of malignant gliomas.
  
  
  METHODS
  We selectively inhibited EGFR and HER2 in glioblastoma cell lines via EGFR- and HER2-specific siRNAs and through the binding of the therapeutic antibodies cetuximab and trastuzumab. The expression of EGFR and HER2 was verified by real-time PCR and western blot analyses. We examined the growth rate, cell cycle distribution, cell migration, clonogenic survival, and radiosensitivity of U251MG and LN-229 glioblastoma cell lines to determine the physiological and cell biological effects of EGFR and HER2 targeting.
  
  
  RESULTS
  EGFR and HER2 targeting using the therapeutic antibodies cetuximab and trastuzumab had no effect on cellular growth rate, cell cycle distribution, cell migration, clonogenic survival, and radiosensitivity in the cell lines U251 and LN-229. In contrast, siRNA knock-down of EGFR and HER2, reduced the growth rate by 40-65 %. The knock-down of EGFR did not change the cell migration rate in the cell lines U251 and LN-229. However, knock-down of HER2 reduced the cell migration rate by 50 %. Radiobiological analysis revealed that EGFR knock-down induced no radiosensitization in U251MG and LN-229 cells. However, the knock-down of HER2 induced radiosensitization in U251MG cells.
  
  
  CONCLUSIONS
  The epidermal growth factor receptor HER2 is a promising anti-tumor target for the therapy of glioblastoma. HER2 targeting may represent a promising strategy to induce cell physiological and radiobiological anti-tumor effects in glioblastoma.
authors.affiliation: Department of Radiotherapy, Martin-Luther-University Halle-Wittenberg, Halle, Germany, henri.wichmann@uk-halle.de.
authors.forename: Henri
authors.initials: H
authors.lastname: Wichmann
authors.forename: Antje
authors.initials: A
authors.lastname: Güttler
authors.forename: Matthias
authors.initials: M
authors.lastname: Bache
authors.forename: Helge
authors.initials: H
authors.lastname: Taubert
authors.forename: Swetlana
authors.initials: S
authors.lastname: Rot
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Kessler
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Eckert
authors.forename: Matthias
authors.initials: M
authors.lastname: Kappler
authors.forename: Dirk
authors.initials: D
authors.lastname: Vordermark
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D000068818:Cetuximab; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D055785:Gene Knockdown Techniques; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D034741:RNA, Small Interfering / Q000494:pharmacology*; D011836:Radiation Tolerance / Q000187:drug effects / Q000528:radiation effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors*; D000068878:Trastuzumab; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000528:radiation effects; D014410:Tumor Stem Cell Assay
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068818:Cetuximab; D066246:ErbB Receptors; D034741:RNA, Small Interfering; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C512478:EGFR protein, human; C508053:ERBB2 protein, human