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Reactive oxygen species activation of MAPK pathway results in VEGF upregulation as an undesired irradiation response
Author(s) -
Drigotas Martynas,
Affolter Annette,
Mann Wolf J.,
Brieger Juergen
Publication year - 2013
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/jop.12056
Subject(s) - downregulation and upregulation , chemistry , reactive oxygen species , mapk/erk pathway , microbiology and biotechnology , biochemistry , signal transduction , biology , gene
Background Radioresistance limits the effectiveness of radiotherapy in head and neck squamous cell carcinoma. We previously demonstrated post‐radiogenic mitogen‐activated protein kinase ( MAPK ) pathway activation and vascular endothelial growth factor ( VEGF ) release resulting in reduced tumor cell response. Here, we examined the association of this mechanism with the induction of reactive oxygen species ( ROS ) under irradiation ( IR ). Methods Intracellular ROS after IR were measured. We modeled radiation‐induced ROS by exposure of two SCC lines to H 2 O 2 and evaluated the impact of irradiation and ROS on ERK phosphorylation by Western blot, immunohistochemistry, and ELISA . Results We found elevated pERK levels after treatment with IR and H 2 O 2 , which could be distinctly suppressed by U0126. Immunohistochemistry and ELISA revealed increased intracellular VEGF levels after H 2 O 2 application. Conclusions Our data show that irradiation‐induced ROS activate the MAPK pathway and release of VEGF . As VEGF is known to be released after cellular distress resulting in cytoprotection, the described mechanism is potentially of importance for therapy success.