Artikel
Activation of Mark-Pathways in head and neck squamous cell carcinomas after irradiation: part of a rescue mechanism?
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Veröffentlicht: | 22. Juli 2009 |
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Gliederung
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Introduction: Irradiation is a fundamental part of head and neck squamous cell carcinoma (HNSCC) therapy. However, tumour response is limited. We analyzed intracellular signalling pathways which are stimulated by irradiation, in particular MAPK cascades. The aim was to define potentially activated rescue mechanisms in tumour cells.
Methods: A HNSCC cell line was used as a model system. Cells were irradiated with a single dosage of 8 Gy. After cell lysis the acitvation of MAPK pathways was analysed using a commercially available array. Results were confirmed and refined by Western blot analysis. Colony forming assays were performed to determine the influence of the ERK cascade on tumour cell survival. The application of the specific ERK inhibitor U0126 enabled us to compare and specify the cellular responses to irradiation.
Results: We observed a pronounced and time-dependent ERK-stimulation equatable with the activation of survival mechanisms in HNSCC cells. Inhibition of the pathway resulted in decreased irradiation resistance.
Conclusions: Irradiation is supposed to induce a strong intracellular response in HNSCC cells. We suggest that the activated ERK pathway is involved in resistance mechanism of this tumour entity.
Hence, the application of specific kinase inhibitors might contribute to overcome irradiation resistance.