Regulated expression of a diphtheria toxin A-chain gene transfected into human cells: possible strategy for inducing cancer cell suicide.
Regulated expression of a diphtheria toxin A-chain gene transfected into human cells: possible strategy for inducing cancer cell suicide.
复制标题
转染人类细胞的白喉毒素 A 链基因的调节表达：诱导癌细胞自杀的可能策略。
作者：
I. Maxwell;F. Maxwell;L. Glodé
作为将植物或细菌毒素导向表面受体的替代方案，我们正在研究通过表达外源引入的毒素基因（即，细胞自杀）。因此，组织特异性基因调控元件可能被用来实现选择性杀伤。为了评估这种方法的可行性，我们用含有白喉毒素A链（DT-A）编码序列的质粒转染了人类细胞（HeLa，B-淋巴母细胞和293细胞）。DT-A序列的存在降低了氯霉素乙酰转移酶从共转染质粒pSV 2cat的瞬时表达水平。通过在DT-A质粒中包含免疫球蛋白增强子，B细胞中的这种表达水平进一步降低。在与DT-A质粒缺乏增强子的共转染实验中，氯霉素乙酰转移酶表达在293细胞（表达腺病毒E1 A和E1 B产物）中比在其他细胞类型中受到更强烈的抑制;此外，DT-A序列的存在消除了用含有neo选择标记的质粒转染后G418抗性293细胞转化体的恢复。这些结果表明，可以利用细胞特异性调节机制，通过表达引入的毒素基因来实现选择性细胞杀伤。
As an alternative to directing plant or bacterial toxins to surface receptors, we are investigating the possibility of killing tumor cells by the expression of an exogenously introduced toxin gene (i.e., cell suicide). Tissue-specific gene regulatory elements might thus be exploited to achieve selective killing. To assess the feasibility of such an approach, we have transfected human cells (HeLa, B-lymphoblastoid, and 293 cells) with plasmids containing the diphtheria toxin A-chain (DT-A) coding sequence. The presence of the DT-A sequence lowered the level of transient expression of chloramphenicol acetyltransferase from a cotransfected plasmid, pSV2cat. This expression level in B-cells was further diminished by the inclusion of an immunoglobulin enhancer in the DT-A plasmid. In cotransfection experiments with a DT-A plasmid lacking an enhancer, chloramphenicol acetyltransferase expression was much more strongly inhibited in 293 cells (which express adenovirus E1A and E1B products) than in the other cell types; furthermore, the presence of the DT-A sequence eliminated recovery of G418-resistant 293 cell transformants after transfection with a plasmid containing the neo selectable marker. These results suggest that cell-specific regulatory mechanisms can be exploited to achieve selective cell killing by expression of an introduced toxin gene.
影响因子：
56.9
作者：
EPHRUSSI, A;CHURCH, GM;GILBERT, W
通讯作者：
GILBERT, W
免疫球蛋白重链增强剂需要一种或多种组织特异性因子。
DOI：
10.1126/science.3917575
发表时间：
1985
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Mercola,M;Goverman,J;Mirell,C;Calame,K
通讯作者：
Calame,K