| He Xin,Meng Qinghui,Meng Aimin,Liu Qiang,Wang Haichao,Fan Saijun.HMGB1 increases radiosensitivity by interacting with HDAC1[J].Chinese Journal of Radiological Medicine and Protection,2015,35(1):8-14 |
| HMGB1 increases radiosensitivity by interacting with HDAC1 |
| Received:December 04, 2014 |
| DOI：10.3760/cma.j.issn.0254-5098.2015.01.002 |
| KeyWords:High mobility group box Radiosensitivity Histone deacetylase 1 Human breast cancer |
| FundProject:This work was supported by grants from National Natural Science Foundation of China (81071906, 81172127 and 81402541). |
| Author Name | Affiliation | E-mail | | He Xin | Key laboratory of Radiation Medicine and Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences, China, Tianjin 100092 | | | Meng Qinghui | Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, USA | | | Meng Aimin | Key laboratory of Radiation Medicine and Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences, China, Tianjin 100092 | | | Liu Qiang | Key laboratory of Radiation Medicine and Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences, China, Tianjin 100092 | | | Wang Haichao | The Feinstein Institute for Medical Research, Manhasset, NY, USA | | | Fan Saijun | Key laboratory of Radiation Medicine and Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences, China, Tianjin 100092 | fansaijun@irm-cams.ac.cn |
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| Abstract:: |
| Objective To study the nuclear protein association of high-mobility group box-1(HMGB1) and histone deacetylase 1(HDAC1), and the effect of interaction on radiosensitivity in human breast cancer cells.Methods The protein-protein interaction was determined by immunoprecipitation-Western blot and glutathione-S-transferase capture assays. Cell growth was examined by MTT (methyl thiazolyl tetrazolium)assay and clonogenic assay. Histone deacetylase activity was analyzed by histone deacetylase assay. Results A significant increase of HMGB1 protein and radiosensitivity was observed in MDA-MB-231 and MDA-MB-468 cells transfected with a pCMV-Tag2B expression vector carrying with a full-length of HMGB1 cDNA. HMGB1 binding to HDAC1 was demonstrated as GST(glutathione S-transferase)-pull down and immunoprecipitation Western blot assay, and the association was elevated by irradiation. An LXCXE motif was required for the HMGB1-HADC1 interaction and HMGB1 radiosensitization. A significant difference of IC50 value was observed, for example, 1.8 and 2.2 Gy(wtHMGB1 transfectants, P<0.05), 3.6 and 3.8 Gy(HMGB1/C103F transfectants, P>0.05), both compared with 3.9 and 4.1 Gy(pCMV-Tag2B transfectants) in MDA-MB-231 and MDA-MB-468 cells, respectively. A specific HDAC1 inhibitor trichostatin A markedly reduced the HMGB1-mediated radiosensitivity, 0.5 Gy in the presence of trichostatin A versus 1.8 Gy in absence of trichostatin A in MDA-MB-231 transfectants, 1.2 Gy (with trichostatin A) versus 2.2 Gy (without trichostatin A) in MDA-MB-468 transfectants, P<0.05. Histone deacetylase activity was also detected in immunoprecipitates prepared from these cells with antibodies to HMGB1, and this activity was abolished by the histone trichostatin A. Conclusions These results suggest a previous unanticipated role for HDAC1 in modification of HMGB1-mediated radiosensitivity by its direct interaction with HMGB1. |
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