Radiosensitization of HNSCC cells by EGFR inhibition depends on the induction of cell cycle arrests
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Radiosensitization of HNSCC cells by EGFR inhibition depends on the induction of cell cycle arrests. / Kriegs, Malte; Kasten-Pisula, Ulla; Riepen, Britta; Hoffer, Konstantin; Struve, Nina; Myllynen, Laura; Braig, Friederike; Binder, Mascha; Rieckmann, Thorsten; Grénman, Reidar; Petersen, Cordula; Dikomey, Ekkehard; Rothkamm, Kai.
In: ONCOTARGET, Vol. 7, No. 29, 19.07.2016, p. 45122-45133.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Radiosensitization of HNSCC cells by EGFR inhibition depends on the induction of cell cycle arrests
AU - Kriegs, Malte
AU - Kasten-Pisula, Ulla
AU - Riepen, Britta
AU - Hoffer, Konstantin
AU - Struve, Nina
AU - Myllynen, Laura
AU - Braig, Friederike
AU - Binder, Mascha
AU - Rieckmann, Thorsten
AU - Grénman, Reidar
AU - Petersen, Cordula
AU - Dikomey, Ekkehard
AU - Rothkamm, Kai
PY - 2016/7/19
Y1 - 2016/7/19
N2 - The increase in cellular radiosensitivity by EGF receptor (EGFR) inhibition has been shown to be attributable to the induction of a G1-arrest in p53-proficient cells. Because EGFR targeting in combination with radiotherapy is used to treat head and neck squamous cell carcinomas (HNSCC) which are predominantly p53 mutated, we tested the effects of EGFR targeting on cellular radiosensitivity, proliferation, apoptosis, DNA repair and cell cycle control using a large panel of HNSCC cell lines. In these experiments EGFR targeting inhibited signal transduction, blocked proliferation and induced radiosensitization but only in some cell lines and only under normal (pre-plating) conditions. This sensitization was not associated with impaired DNA repair (53BP1 foci) or induction of apoptosis. However, it was associated with the induction of a lasting G2-arrest. Both, the radiosensitization and the G2-arrest were abrogated if the cells were re-stimulated (delayed plating) with actually no radiosensitization being detectable in any of the 14 tested cell lines. Therefore we conclude that EGFR targeting can induce a reversible G2 arrest in p53 deficient HNSCC cells, which does not consequently result in a robust cellular radiosensitization. Together with recent animal and clinical studies our data indicate that EGFR inhibition is no effective strategy to increase the radiosensitivity of HNSCC cells.
AB - The increase in cellular radiosensitivity by EGF receptor (EGFR) inhibition has been shown to be attributable to the induction of a G1-arrest in p53-proficient cells. Because EGFR targeting in combination with radiotherapy is used to treat head and neck squamous cell carcinomas (HNSCC) which are predominantly p53 mutated, we tested the effects of EGFR targeting on cellular radiosensitivity, proliferation, apoptosis, DNA repair and cell cycle control using a large panel of HNSCC cell lines. In these experiments EGFR targeting inhibited signal transduction, blocked proliferation and induced radiosensitization but only in some cell lines and only under normal (pre-plating) conditions. This sensitization was not associated with impaired DNA repair (53BP1 foci) or induction of apoptosis. However, it was associated with the induction of a lasting G2-arrest. Both, the radiosensitization and the G2-arrest were abrogated if the cells were re-stimulated (delayed plating) with actually no radiosensitization being detectable in any of the 14 tested cell lines. Therefore we conclude that EGFR targeting can induce a reversible G2 arrest in p53 deficient HNSCC cells, which does not consequently result in a robust cellular radiosensitization. Together with recent animal and clinical studies our data indicate that EGFR inhibition is no effective strategy to increase the radiosensitivity of HNSCC cells.
U2 - 10.18632/oncotarget.9161
DO - 10.18632/oncotarget.9161
M3 - SCORING: Journal article
C2 - 27281611
VL - 7
SP - 45122
EP - 45133
JO - ONCOTARGET
JF - ONCOTARGET
SN - 1949-2553
IS - 29
ER -