EGFRvIII does not affect radiosensitivity with or without gefitinib treatment in glioblastoma cells
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Nina Struve1, Matthias Riedel1, Alexander Schulte2, Thorsten Rieckmann1,3, Tobias J. Grob4, Andreas Gal5, Kai Rothkamm1, Katrin Lamszus2, Cordula Petersen1, Ekkehard Dikomey1, Malte Kriegs1
1Department of Radiotherapy and Radio-Oncology, University Medical Center Hamburg Eppendorf, Hamburg, Germany
2Department of Neurosurgery, University Medical Center Hamburg Eppendorf, Hamburg, Germany
3Department of Otorhinolaryngology and Head and Neck Surgery, University Medical Center Hamburg Eppendorf, Hamburg, Germany
4Department of Pathology, University Medical Center Hamburg Eppendorf, Hamburg, Germany
5Department of Human Genetics, University Medical Center Hamburg Eppendorf, Hamburg, Germany
Malte Kriegs, e-mail: [email protected]
Nina Struve, e-mail: [email protected]
Keywords: EGFRvIII, glioblastoma, radiosensitivity, X-irradiation, gefitinib
Received: August 10, 2015 Accepted: September 04, 2015 Published: September 16, 2015
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.
Conclusion: The data indicate that EGFRvIII does not alter radiosensitivity with or without anti-EGFR treatment.
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