دورية أكاديمية
In HPV-Positive HNSCC Cells, Functional Restoration of the p53/p21 Pathway by Proteasome Inhibitor Bortezomib Does Not Affect Radio- or Chemosensitivity
العنوان: | In HPV-Positive HNSCC Cells, Functional Restoration of the p53/p21 Pathway by Proteasome Inhibitor Bortezomib Does Not Affect Radio- or Chemosensitivity |
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المؤلفون: | Steve Seltzsam, Frank Ziemann, Kristin Dreffke, Stefanie Preising, Andrea Arenz, Ulrike Schötz, Rita Engenhart-Cabillic, Ekkehard Dikomey, Andrea Wittig |
المصدر: | Translational Oncology, Vol 12, Iss 3, Pp 417-425 (2019) |
بيانات النشر: | Elsevier |
سنة النشر: | 2019 |
المجموعة: | Directory of Open Access Journals: DOAJ Articles |
مصطلحات موضوعية: | Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
الوصف: | Human papillomavirus (HPV) associated squamous cell carcinomas of the head and neck region (HPV+ HNSCCs) harbor diverging biological features as compared to classical noxa-induced (HPV−) HNSCC. One striking difference between subtypes is that the tumor suppressor gene TP53 is usually not mutated in HPV+ HNSCCs. However, p53 is inhibited by viral oncoprotein E6, leading to premature proteasomal degradation. We asked whether bortezomib (BZM), a clinically approved inhibitor of the proteasome, can functionally restore p53 and investigated in how far this will result in an enhanced radio- or chemosensitivity of HPV+ HNSCC cell lines. For all four HPV+ cell lines tested, BZM led to functional restoration of p53 and transactivation of downstream protein p21. In HPV+ cells, BZM also restored the radiation-induced p53/p21 transactivation. Consistently, in HPV+ cells, a restored G1 arrest as well as enhanced apoptosis were seen when BZM was given prior to irradiation (IR) or cisplatin (CDDP). BZM alone reduced the clonogenic survival of both HPV− and HPV+ cells. However, if BZM was combined with IR or CDDP, BZM did not significantly enhance radio- or chemosensitivity of HPV+ or HPV− HNSCC cell lines. |
نوع الوثيقة: | article in journal/newspaper |
اللغة: | English |
تدمد: | 1936-5233 |
العلاقة: | http://www.sciencedirect.com/science/article/pii/S1936523318304881Test; https://doaj.org/toc/1936-5233Test; https://doaj.org/article/f807cc6af8ea44a5961abf758c4068a7Test |
DOI: | 10.1016/j.tranon.2018.11.013 |
الإتاحة: | https://doi.org/10.1016/j.tranon.2018.11.013Test https://doaj.org/article/f807cc6af8ea44a5961abf758c4068a7Test |
رقم الانضمام: | edsbas.1B253187 |
قاعدة البيانات: | BASE |
تدمد: | 19365233 |
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DOI: | 10.1016/j.tranon.2018.11.013 |