Abstract 1664: A delicate balance between radiation-induced autophagy and apoptosis in HPV-positive head and neck cancer
| العنوان: | Abstract 1664: A delicate balance between radiation-induced autophagy and apoptosis in HPV-positive head and neck cancer |
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| المؤلفون: | Bryan Bednarz, Randall J. Kimple, Reza Djavadian, Kai D. Ludwig, Tyler L. Fowler |
| المصدر: | Cancer Research. 73:1664-1664 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Cancer Research, Autophagy, Head and neck cancer, Acridine orange, Cancer, Biology, medicine.disease, Blot, chemistry.chemical_compound, Oncology, Downregulation and upregulation, chemistry, Cell culture, Apoptosis, Immunology, Cancer research, medicine |
| الوصف: | Purpose: The molecular mechanisms responsible for improved outcomes seen in patients with human papillomavirus (HPV) positive head and neck cancer (HNC) remain largely unknown. Ionizing radiation can induce autophagy, a genetically programmed, evolutionarily conserved response to stress whereby cellular constituents are engulfed, digested, and recycled to sustain cellular metabolism. We investigated whether radiation-induced cellular autophagy is modulated by HPV oncogenes leading to altered therapeutic responses between HPV+ and HPV- HNCs. Methods: An immortalized human tonsillar epithelial (HTE) cell line engineered to stably express LXSN vector alone, HPV-16 E6, or HPV-16 E7 was used for all experiments. All constructs received a single radiation dose of 4 Gy. Radiation survival was assessed by clonogenic survival. Activation of autophagy proteins LC3-A and LC3-B were analyzed at 4 and 24 hr time points using western blotting and fluorescence microscopy along with acridine orange staining. Apoptosis was evaluated by caspase activity at the same time points. Results: HPV-16 E6 resulted in greater sensitivity, while HPV-16 E7 resulted in radiation resistance relative to than control cells (surviving fraction after 4 Gy = 8.4+/-0.5% vs. 35+/-3.8% vs. 20+/-1.1%, respectively, 1way ANOVA p Conclusions: The HPV oncoproteins E7 up regulates autophagic pathways at baseline correlating with radiation resistance. Four hours following radiation, both E6 and E7 result in significant upregulation of autophagy. This is followed by upregulation of apoptosis, suggesting a transition from an initial protective response to cellular death. Citation Format: Tyler L. Fowler, Kai D. Ludwig, Reza Djavadian, Bryan P. Bednarz, Randall J. Kimple. A delicate balance between radiation-induced autophagy and apoptosis in HPV-positive head and neck cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1664. doi:10.1158/1538-7445.AM2013-1664 |
| تدمد: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am2013-1664 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::5f1903be334dde337082c211d5d22e1a https://doi.org/10.1158/1538-7445.am2013-1664 |
| رقم الانضمام: | edsair.doi...........5f1903be334dde337082c211d5d22e1a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15387445 00085472 |
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| DOI: | 10.1158/1538-7445.am2013-1664 |