Activation of mitogen-activated protein kinase extracellular signal-related kinase in head and neck squamous cell carcinomas after irradiation as part of a rescue mechanism

6533b829fe1ef96bd128ae8c

RESEARCH PRODUCT

Activation of mitogen-activated protein kinase extracellular signal-related kinase in head and neck squamous cell carcinomas after irradiation as part of a rescue mechanism

Annette Affolter Jürgen Brieger Kai Fruth Schmidtmann Irene Wolf J. Mann Christoph Brochhausen

subject

Vascular Endothelial Growth Factor A MAPK/ERK pathway MAP Kinase Signaling System Mice Nude Mice chemistry.chemical_compound Cell Line Tumor Radioresistance Nitriles Butadienes medicine Animals Humans Enzyme Inhibitors Extracellular Signal-Regulated MAP Kinases Protein kinase A biology Kinase business.industry Radiotherapy Dosage medicine.disease Immunohistochemistry Head and neck squamous-cell carcinoma Up-Regulation Vascular endothelial growth factor Otorhinolaryngology chemistry Head and Neck Neoplasms Mitogen-activated protein kinase Carcinoma Squamous Cell Cancer research biology.protein Mitogen-Activated Protein Kinases Signal transduction business Neoplasm Transplantation Signal Transduction

description

Background. Irradiation plays a pivotal role in head and neck squamous cell carcinoma (HNSCC) treatment. However, especially recurrent tumors frequently show increased radioresistance. We analyzed irradiation-stimulated mitogen-activated protein kinase (MAPK) signaling pathways to define cellular rescue mechanisms. Methods. Irradiated HNSCC cells were screened for MAPK activation and results were confirmed and refined by functional analyses. Extracellular signal-regulated kinase (ERK) inhibitor U0126 application enabled us to specify postradiogenic cellu- lar responses. Vascular endothelial growth factor (VEGF) levels were analyzed additionally. Results. We observed a pronounced and time-dependent ERK stimulation. Pathway inhibition resulted in decreased radioresistance. Likewise, we found a decrease of VEGF release after inhibitor treatment. ERK activation was confirmed in xenotransplants showing elevated postradiogenic phospho- ERK (pERK) and VEGF levels. Conclusions. Our data give evidence for induction of ERK and successive VEGF release in HNSCC during radiotherapy, which might be partially explained by autoregulated cytopro- tection maintained by pERK and potentially VEGF. In conclu- sion, targeting the ERK-VEGF axis might enhance the efficiency of radiotherapy. V

year	journal	country	edition	language
2010-04-23	Head & Neck

https://doi.org/10.1002/hed.21623