Inducible promoters for gene therapy of head and neck cancer: an in vitro study
Inducible promoters for gene therapy of head and neck cancer: an in vitro study
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头颈癌基因治疗的诱导启动子：一项体外研究
DOI：
10.1007/s00405-003-0621-z
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
F. Hoppe
中科院分区：
文献类型：
--
作者：
M. Schmidt;T. Heimberger;Petra Gruensfelder;Gabriele Schler;F. Hoppe
基因治疗的目的包括对转基因表达进行严格的时空控制。有几种方法涉及用于控制自杀基因的外部诱导基因启动子。可能在头颈部肿瘤基因治疗中发挥作用的两个启动子是高温诱导的人类热休克蛋白-70(HSP70)启动子和早期生长反应-1基因(EGR-1)的辐射诱导启动子。我们在体外检测了HSP-70启动子和含有合成的EGR-1增强子的放射反应元件的启动子对两个稳定转染头颈部癌细胞系报告基因表达的影响，并通过流式细胞仪分析、免疫印迹分析和荧光显微镜检测了基因激活的成功率。有了HSP70启动子，我们在两个被测试的细胞系中的一个细胞中，经过高温处理后，报告基因的表达增加了5.83倍。辐射诱导的构建只显示了弱的基因诱导，并且具有高背景表达的特点。这两个系统都以高度依赖细胞类型的方式工作。重点讨论了外源诱导型转基因表达在头颈癌基因治疗中的临床应用。
The aim of gene therapy includes the tight spatial and temporal control of transgenic expression. There are several approaches concerning externally inducible gene promoters used for the control of suicide genes. Two of the promoters that might play a role in head and neck cancer gene therapy are the hyperthermia-inducible human heat shock protein-70 (hsp70) promotor, as well as the radiation-inducible promoter of the early growth response-1 gene (egr-1). We tested the hsp-70 promoter as well as a promoter construct, containing synthetic radio-responsive elements of the egr-1 enhancer for the effect on reporter gene expression in two stably transfected head and neck carcinoma cell lines in vitro and measured the success of gene activation by FACS analysis, western blot analysis and fluorescence microscopy. With the hsp70 promoter we reached a 5.83-fold increase of reporter gene expression after hyperthermic treatment in one of the two cell lines tested. The radiation-inducible construct revealed only weak gene induction and was marked by high background expression. Both systems worked in a highly cell-type dependent manner. The possible clinical use of externally inducible transgene expression in head and neck carcinoma gene therapy is critically discussed.
腺病毒介导的热诱导双自杀基因转移至前列腺癌细胞中。
DOI：
--
发表时间：
1998
期刊：
Cancer research.
影响因子：
--
作者：
Blackburn,RV;Galoforo,SS;Corry,PM;Lee,YJ
通讯作者：
Lee,YJ
DOI：
10.1073/pnas.89.21.10149
发表时间：
1992-11-01
影响因子：
11.1
作者：
DATTA, R;RUBIN, E;KUFE, DW
通讯作者：
KUFE, DW