Depletion of the type 1 IGF receptor delays repair of radiation-induced DNA double strand breaks
<h4>Background and purpose:</h4> <p>IGF-1R depletion sensitizes prostate cancer cells to ionizing radiation and DNAdamaging cytotoxic drugs. This study investigated the hypothesis that IGF-1R regulates DNA double strand break (DSB) repair.</p> <h4>Methods:</h4> &l...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Elsevier
2012
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| _version_ | 1826288206726823936 |
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| author | Turney, B Kerr, M Chitnis, M Lodhia, K Wang, Y Riedemann, J Rochester, M Protheroe, A Brewster, S Macaulay, V |
| author_facet | Turney, B Kerr, M Chitnis, M Lodhia, K Wang, Y Riedemann, J Rochester, M Protheroe, A Brewster, S Macaulay, V |
| author_sort | Turney, B |
| collection | OXFORD |
| description | <h4>Background and purpose:</h4> <p>IGF-1R depletion sensitizes prostate cancer cells to ionizing radiation and DNAdamaging cytotoxic drugs. This study investigated the hypothesis that IGF-1R regulates DNA double strand break (DSB) repair.</p> <h4>Methods:</h4> <p>We tested effects of IGF-1R siRNA transfection on the repair of radiation-induced DSBs by immunoblotting and immunofluorescence for cH2AX, and pulsed-field gel electrophoresis. Homologous recombination (HR) was quantified by reporter assays, and cell cycle distribution by flow cytometry.</p> <h4>Results:</h4> <p>We confirmed that IGF-1R depletion sensitized DU145 and PC3 prostate cancer cells to ionizing radiation. DU145 control transfectants resolved radiation-induced DSBs within 24 h, while IGF-1R depleted cells contained 30–40% unrepaired breaks at 24 h. IGF-1R depletion induced significant reduction in DSB repair by HR, although the magnitude of the repair defect suggests additional contributory factors. Radiation-induced G2-M arrest was attenuated by IGF-1R depletion, potentially suppressing cell cycle-dependent processes required for HR. In contrast, IGF-1R depletion induced only minor radiosensitization in LNCaP cells, and did not influence repair. Cell cycle profiles were similar to DU145, so were unlikely to account for differences in repair responses.</p> <h4>Conclusions:</h4> <p>These data indicate a role for IGF-1R in DSB repair, at least in part via HR, and support use of IGF-1R inhibitors with DNA damaging cancer treatments.</p> |
| first_indexed | 2024-03-07T02:10:13Z |
| format | Journal article |
| id | oxford-uuid:a06051f2-a64e-4cd3-b3aa-6f5cf8176cf6 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:10:13Z |
| publishDate | 2012 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:a06051f2-a64e-4cd3-b3aa-6f5cf8176cf62022-03-27T02:05:06ZDepletion of the type 1 IGF receptor delays repair of radiation-induced DNA double strand breaksJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a06051f2-a64e-4cd3-b3aa-6f5cf8176cf6EnglishSymplectic Elements at OxfordElsevier2012Turney, BKerr, MChitnis, MLodhia, KWang, YRiedemann, JRochester, MProtheroe, ABrewster, SMacaulay, V<h4>Background and purpose:</h4> <p>IGF-1R depletion sensitizes prostate cancer cells to ionizing radiation and DNAdamaging cytotoxic drugs. This study investigated the hypothesis that IGF-1R regulates DNA double strand break (DSB) repair.</p> <h4>Methods:</h4> <p>We tested effects of IGF-1R siRNA transfection on the repair of radiation-induced DSBs by immunoblotting and immunofluorescence for cH2AX, and pulsed-field gel electrophoresis. Homologous recombination (HR) was quantified by reporter assays, and cell cycle distribution by flow cytometry.</p> <h4>Results:</h4> <p>We confirmed that IGF-1R depletion sensitized DU145 and PC3 prostate cancer cells to ionizing radiation. DU145 control transfectants resolved radiation-induced DSBs within 24 h, while IGF-1R depleted cells contained 30–40% unrepaired breaks at 24 h. IGF-1R depletion induced significant reduction in DSB repair by HR, although the magnitude of the repair defect suggests additional contributory factors. Radiation-induced G2-M arrest was attenuated by IGF-1R depletion, potentially suppressing cell cycle-dependent processes required for HR. In contrast, IGF-1R depletion induced only minor radiosensitization in LNCaP cells, and did not influence repair. Cell cycle profiles were similar to DU145, so were unlikely to account for differences in repair responses.</p> <h4>Conclusions:</h4> <p>These data indicate a role for IGF-1R in DSB repair, at least in part via HR, and support use of IGF-1R inhibitors with DNA damaging cancer treatments.</p> |
| spellingShingle | Turney, B Kerr, M Chitnis, M Lodhia, K Wang, Y Riedemann, J Rochester, M Protheroe, A Brewster, S Macaulay, V Depletion of the type 1 IGF receptor delays repair of radiation-induced DNA double strand breaks |
| title | Depletion of the type 1 IGF receptor delays repair of radiation-induced DNA double strand breaks |
| title_full | Depletion of the type 1 IGF receptor delays repair of radiation-induced DNA double strand breaks |
| title_fullStr | Depletion of the type 1 IGF receptor delays repair of radiation-induced DNA double strand breaks |
| title_full_unstemmed | Depletion of the type 1 IGF receptor delays repair of radiation-induced DNA double strand breaks |
| title_short | Depletion of the type 1 IGF receptor delays repair of radiation-induced DNA double strand breaks |
| title_sort | depletion of the type 1 igf receptor delays repair of radiation induced dna double strand breaks |
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