| LI Xin-li,MENG Qing-hui,Eliot M Rosen,et al.Effect of UHRF1 on radiosensitivity of human breast cancer cells to X-rays and its mechanisms[J].Chinese Journal of Radiological Medicine and Protection,2010,30(6):654-657 |
| Effect of UHRF1 on radiosensitivity of human breast cancer cells to X-rays and its mechanisms |
| Received:July 13, 2010 |
| DOI： |
| KeyWords:UHRF1 Breast Cancer Radiosensitivity |
| FundProject:国家自然科学基金(81001185);长江学者和创新团队发展计划资助(IRT0849);苏州市基础研究计划项目(YJS0905);江苏省高校自然科学基金(10KJB310011) |
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| Abstract:: |
| Objective To investigate the effect of UHRF1 on the radiosensitivity to χ-ray in human breast cancer MDA-MB-231 cells and the underlying mechanisms. Methods Cell survival was determined by colony formation assay. Cell cycle distribution was measured by flow cytometry. The apoptosis was evaluated by DNA fragmentation assay and Annexin V apoptosis detection kit. Protein expression was analyzed by Western blot, and chromosome aberration (centric rings and dicentrics) were observed by conventional chromosome analysis. Results A significant decrease of radiosensitivity to X-rays was observed in MDA-MB-231 cells transfected with a full-length of human UHRF1 cDNA (MDA-MB-231/UHRF1) compared with the control cells (MDA-MB-231/parental and MDA-MB-231/Neo), and the D0 value increased from 2.08 to 3.17 Gy after UHRF1 transfection. In contrast, a decreased expression of UHRF1 by a specific UHRF1-siRNA significantly decreased cell survival from 41% to 17%. The UHRF1-mediated radioresistance was correlated with a G2/M arrest, a decreased apoptosis rate, a down-regulation of the pro-apoptotic protein Bax and up-regulation of the DNA damage repair proteins Ku70 and Ku80. Furthermore, chromosomal aberrations (centric rings and dicentrics) by X-ray were less in MDA-MB-231/UHRF1 than those in MDA-MB-231/parental cells and MDA-MB-231/Neo control cells. Conclusion UHRF1 may be a new target in the radiotherapy of breast cancer via affecting apoptosis and DNA damage repair. |
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