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81st Annual Meeting of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery

German Society of Oto-Rhino-Laryngology, Head and Neck Surgery

12.05. - 16.05.2010, Wiesbaden

Influence of activating Ras-mutations on radioresistance mechanisms in epithelial cancer cells

Meeting Abstract

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  • corresponding author presenting/speaker Annette Affolter - Hals-Nasen-Ohren-Klinik der Johannes-Gutenberg-Universität Mainz, Germany
  • Wolf J. Mann - Hals-Nasen-Ohren-Klinik der Johannes-Gutenberg-Universität Mainz, Germany
  • Jürgen Brieger - Hals-Nasen-Ohren-Klinik der Johannes-Gutenberg-Universität Mainz, Germany

German Society of Oto-Rhino-Laryngology, Head and Neck Surgery. 81st Annual Meeting of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery. Wiesbaden, 12.-16.05.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. Doc10hno023

DOI: 10.3205/10hno023, URN: urn:nbn:de:0183-10hno0235

Published: July 6, 2010

© 2010 Affolter et al.
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Outline

Text

Irradiation- stimulated signalling via the two pathways Raf-MEK-ERK and PI3K/Akt is known to be closely associated with a limited response to radiotherapy in HNSCC. In the present study, we have addressed the question whether the K-Ras mutation G12S causing constitutive activation of ERK and Akt is responsible for enhanced radioresistance in epithelial tumour cells.

We used two epithelial tumour cell lines as a model system, one of them harbouring a G12S K-Ras mutation. Cells were irradiated and the effect of combined treatment with ionizing radiation (IR) and inhibitors on the expression of pERK and pAkt was determined by western blotting. Additionally clonogenic assays were performed to functionally analyse survival of the two different cell lines.

We observed the G12S cell line showing a clearly reduced response to inhibitor treatment under iradiation. We hypothesize a postradiogenic constitutive activation of the two pathways which are both required for Ras-mediated radioresistance in epithelial cells. If this effect should prove itself as a general mechanism in Ras-mutated tumours, application of specific inhibitors to block both cascades in parallel could contribute to enhance radiosensitivity in these types of cancer.