| 熊杰,周云峰,孙文洁,王伟峰,廖正凯,周福祥,谢丛华.放射诱导的肿瘤特异性嵌合启动子研究[J].中华放射医学与防护杂志,2010,30(2):152-155 |
| 放射诱导的肿瘤特异性嵌合启动子研究 |
| Study of cancer-specific chimeric promoters induced by irradiation |
| 投稿时间：2009-06-28 |
| DOI： |
| 中文关键词: 人端粒酶反转录酶启动子 CArG元件 基因治疗 |
| 英文关键词:Human telomerase reverse transcriptase gene promoter CArG elements Gene therapy |
| 基金项目:国家自然科学基金(30672438);湖北省创新群体项目(2006ABC009) |
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| 中文摘要: |
| 目的 将放射敏感性的CArG元件与肿瘤特异性的人端粒酶反转录酶(hTERT)基因启动子相结合,构建新的嵌合启动子。方法 构建含不同CArG元件数量的嵌合hTERT启动子,在放射线诱导下(单剂量或分割照射),利用荧光素酶报告基因检测其在肿瘤细胞(HeLa、A549、MHCC97细胞)及正常细胞(hEL细胞)中的活性。结果 包含6个CArG元件的hTERT嵌合启动子较含其他数量CArG的嵌合启动子显示了更好的放射诱导性,并在4～6 Gy时达到顶峰,而构建的嵌合启动子在正常的hEL细胞中活性很低。在肿瘤细胞中,3次2 Gy与单次6 Gy剂量照射相比较,报告基因的表达相当。结论 包含6个CArG元件的肿瘤特异性嵌合启动子具备良好的放射诱导性,这种嵌合的启动子系统具有肿瘤基因治疗的潜力。 |
| 英文摘要: |
| Objective To combine the radio-inducible CArG element with cancer-specific human telomerase reverse transcriptase(hTERT) gene promoter, and to construct the novel chimeric promoters. Methods The synthetic hTERT promoters containing different number of radio-inducible CArG elements were constructed, and the activities of the promoters in the cancer cells (HeLa, A549, and MHCC97 cells) and nomal cells(hEL cells) were detected by using luciferase-reporter assays afer the treatment of irradiation(a single or fractionated irradiation dose). Results Synthetic promoter containing 6 repeated CArG units was better in radio-inducibility than any other promoters containing different number of CArG units, and nearly maximum levels obtained at 4-6 Gy. The very low activities of the chimeric promoters could be detected in normal hEL cells. A similar level of reporter gene expression was observed after 3 fractionated doses of 2 Gy compared with a single dose of 6 Gy in cancer cells. Conclusions The cancer-specific chimeric promoter containing 6 CArG elements showes the best radio-response, and the chimeric promoter system has the potential in cancer gene therapy. |
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