Effects of antisense-based folypoly-gamma-glutamate synthetase down-regulation on reduced folates and cellular proliferation in CCRF-CEM cells.
Effects of antisense-based folypoly-gamma-glutamate synthetase down-regulation on reduced folates and cellular proliferation in CCRF-CEM cells.
复制标题
基于反义的叶聚-γ-谷氨酸合成酶下调对 CCRF-CEM 细胞中叶酸减少和细胞增殖的影响。
DOI：
10.1016/s0006-2952(98)00089-6
复制
发表时间：
1998
影响因子：
5.8
通讯作者：
Priest,DG
中科院分区：
文献类型：
--
作者：
Liu,Y;Raghunathan,K;Hill,C;He,Y;Bunni,MA;Barredo,J;Priest,DG
The effect of down-regulation of folylpoly-γ-glutamate synthetase (FPGS) activity on intracellular reduced folate accumulation and cellular proliferation was examined, using an inducible antisense expression system in the human T-lymphoblastic leukemia cell line CCRF-CEM. FPGS catalyzes the addition of γ-glutamyl residues to natural folates and classical antifolates, which results in their enhanced cellular retention and increased cytotoxicity. As such, this enzyme has become a focus as a potential anticancer drug target. However, direct evidence to support this concept has been elusive. Hence, a study was undertaken using an antisense-based expression system to down-regulate FPGS activity. This inducible expression system was used to demonstrate that lower FPGS activity can lead to substantially lower intracellular folate content, which coincides with suppression of thymidylate synthesis and inhibition of cellular proliferation.
