Article
Radio Sensitivity and Changes in Protein Expression in HPV-positive Head and Neck Cancer Cell Lines
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Published: | July 30, 2013 |
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Aim: Oropharyngeal squamous cell carcinomas (OSCC) are often associated with an infection by human papilloma viruses (HPV). Patients with HPV-positive OSCC are known to respond much better to irradiation and therefore have a better prognosis. Until now, molecular causes for this observation are largely unknown. In this study we analysed the radio sensitivity of HPV positive and negative OSCC cell lines in vitro and examined signaling pathways related to radiation induced apoptosis and cell cycle regulation.
Methods: Surviving fractions of 4 HPV negative and of 4 HPV16 positive immortal OSCC cell lines were determined using colony forming assays after irradiation. Western Blot analyses were performed to compare selected proteins in untreated versus irradiated OSCC cell lines.
Results: Irradiated HPV positive and negative OSCC cell lines revealed significant differences in SF2-values (Surviving Fraction after 2Gy) (p=0,01) and HPV positive cell lines were more sensible to irradiation. Irradiation caused changes in protein expression and in expression kinetics of key regulatory proteins for apoptosis and cell cycle regulation, both in HPV positive and negative OSCC cell lines, but also within each entity.
Conclusion: Increased radio sensitivity of HPV-positive OSCC cell lines reflect the clinical response of HPV-associated OSCC to radiation therapy. Results indicated a difference in the activation of signaling pathways. In comparison to HPV unrelated tumors, irradiation seems to reactivate regulator proteins in HPV positive OSCC, which were previously inhibited via HPV oncoproteins. Thus, HPV positive OSCC seem to be more suitable for targeted therapy in future.