دورية أكاديمية
A novel radiation-induced p53 mutation is not implicated in radiation resistance via a dominant-negative effect.
| العنوان: | A novel radiation-induced p53 mutation is not implicated in radiation resistance via a dominant-negative effect. |
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| المؤلفون: | Sun, Yunguang, Myers, Carey Jeanne, Dicker, Adam, MD, PhD, Lu, MD, Bo |
| المصدر: | Department of Radiation Oncology Faculty Papers |
| بيانات النشر: | Jefferson Digital Commons |
| سنة النشر: | 2014 |
| المجموعة: | Jefferson Digital Commons (Thomas Jefferson University, Philadelphia) |
| مصطلحات موضوعية: | Department of Radiation Oncology, Department of Microbiology and Immunology, Thomas Jefferson University, apoptosis, article, cancer cell, cell cycle arrest, cell survival, clonogenic assay, controlled study, DNA binding, gene deletion, gene sequence, genetic transfection, human, human cell, lung cancer, MTS assay, mutational analysis, protein cleavage, protein domain, protein expression, protein function, protein phosphorylation, radiation dose, radiation mutagenesis, radiosensitivity, sequence analysis, transcription initiation, Oncology |
| الوصف: | Understanding the mutations that confer radiation resistance is crucial to developing mechanisms to subvert this resistance. Here we describe the creation of a radiation resistant cell line and characterization of a novel p53 mutation. Treatment with 20 Gy radiation was used to induce mutations in the H460 lung cancer cell line; radiation resistance was confirmed by clonogenic assay. Limited sequencing was performed on the resistant cells created and compared to the parent cell line, leading to the identification of a novel mutation (del) at the end of the DNA binding domain of p53. Levels of p53, phospho-p53, p21, total caspase 3 and cleaved caspase 3 in radiation resistant cells and the radiation susceptible (parent) line were compared, all of which were found to be similar. These patterns held true after analysis of p53 overexpression in H460 cells; however, H1299 cells transfected with mutant p53 did not express p21, whereas those given WT p53 produced a significant amount, as expected. A luciferase assay demonstrated the inability of mutant p53 to bind its consensus elements. An MTS assay using H460 and H1299 cells transfected with WT or mutant p53 showed that the novel mutation did not improve cell survival. In summary, functional characterization of a radiation-induced p53 mutation in the H460 lung cancer cell line does not implicate it in the development of radiation resistance. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | https://jdc.jefferson.edu/radoncfp/45Test; https://jdc.jefferson.edu/cgi/viewcontent.cgi?article=1048&context=radoncfpTest |
| الإتاحة: | https://jdc.jefferson.edu/radoncfp/45Test https://jdc.jefferson.edu/cgi/viewcontent.cgi?article=1048&context=radoncfpTest |
| رقم الانضمام: | edsbas.90D2DF53 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |