【作者】 刘建香；

【导师】 苏旭；

【作者基本信息】 中国人民解放军军事医学科学院 ， 放射医学， 2004， 博士

【摘要】 本研究根据电离辐射可诱导早期生长反应-1(Egr-1) 基因启动子激活，启动下游基因表达的分子机制和抑癌基因p16的抑瘤作用，构建了含有放射敏感性启动子Egr-1和人源性p16基因的重组表达质粒pEgr-p16。探讨了经pEgr-p16重组质粒转染HeLa细胞和SMMC-7721细胞在60Coγ射线照射后，p16基因的表达及其抑制肿瘤细胞生长中的作用。体外实验研究证实：重组质粒pEgr-p16转染的HeLa细胞和SMMC-7721细胞，接受60Coγ射线照射后p16表达明显高于未转染的HeLa细胞和SMMC-7721细胞。进一步的研究表明：辐射可诱导pEgr-p16重组质粒转染的HeLa细胞和SMMC-7721细胞CDK4、 CyclinD1蛋白表达下调；c-myc基因转录水平下调。由于辐射诱导激活了Egr-1基因启动子，使p16及其相关下游基因表达增强或下调，加之辐射的联合作用，引起HeLa细胞和SMMC-7721细胞发生G2／M期阻滞，最终导致HeLa细胞和SMMC-7721细胞的增殖抑制。本研究结果为探索新的肿瘤治疗方案、提高肿瘤放射治疗效果具有重要的理论意义和实际意义。更多还原

【Abstract】 ExPerimental study on exPression of PEgr-P16 and the role of anti-tumor indueed by ionizing radiation In this study， aeeording to the meehanism that ionizing radiation ean aetivateearly growth resPonse-1(Egr-l)gene Promoter，whieh induees the exPression ofdownstream genes and anti-tumor effeet of a tumor suPPressor gene P16，thus，areeombinant Plasmid whieh eontaining human suPPressor gene P16 andradio-sensitive Promoter(Egr-l)was eonstrueted. It has been demonstrated that 6oeo-rays irradiation ean enhanee theexPression of P16 in HeLa and SMMC-7721 eells whieh were transfeeted byrecombined Plasmids PEgr-P16 in vitro.It was higher than that in HeLa andSMMC-772 1 eells whieh were not transfeeted.The researeh also demonstrated thatradiation ean deerease the exPression of CDK4 and CyelinD 1 Protein level anddeerease the exPression ofe-mye gene transeriPtional level in Hel，a eells andSMMC-772 1 eells whieh were transfeeted by reeombined Plasmids PEgr-P16.Theinerease or deerease of exPression of P16 and eorrelative downstream genesdePends on Egr-1 Promoter that aetivated by ionizing radiation.Theabove-meniioned roles and radiation effeets indueed GZ/M arrest and inhibited eellgrowth in HeLa and SMMC-7721 eells finally. This researeh has an imPortant and Praetieal signifieanee for investigating newtheraPy method that inerease radiotherapeutie effeets on malignant tumor.更多还原