EGFRvIII does not affect radiosensitivity with or without gefitinib treatment in glioblastoma cells

TY - JOUR

T1 - EGFRvIII does not affect radiosensitivity with or without gefitinib treatment in glioblastoma cells

AU - Struve, Nina

AU - Riedel, Matthias

AU - Schulte, Alexander

AU - Rieckmann, Thorsten

AU - Grob, Tobias J

AU - Gal, Andreas

AU - Rothkamm, Kai

AU - Lamszus, Katrin

AU - Petersen, Cordula

AU - Dikomey, Ekkehard

AU - Kriegs, Malte

PY - 2015/10/20

Y1 - 2015/10/20

N2 - 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.

AB - 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.

U2 - 10.18632/oncotarget.5293

DO - 10.18632/oncotarget.5293

M3 - SCORING: Journal article

C2 - 26418954

VL - 6

SP - 33867

EP - 33877

JO - ONCOTARGET

JF - ONCOTARGET

SN - 1949-2553

IS - 32

ER -