Blocking CHK1 expression induces apoptosis and abrogates the G2 checkpoint mechanism

被引：46

作者：

Luo, Y

Rockow-Magnone, SK

Kroeger, PE

Frost, L

Chen, ZH

Han, EKH

Ng, SC

Simmer, RL

Giranda, VL

机构：

[1] Abbott Labs, Pharmaceut Prod Div, Dept 47S AP9A, Canc Res, Abbott Pk, IL 60064 USA

[2] Abbott Labs, Pharmaceut Prod Div, Dept 4MD AP10, Adv Technol, Abbott Pk, IL 60064 USA

[3] Abbott Labs, Pharmaceut Prod Div, Dept 4N6 AP9, Canc Res, Abbott Pk, IL 60064 USA

来源：

NEOPLASIA | 2001年 / 3卷 / 05期

关键词：

Chk1; antisense; ribozyme; checkpoint; chemotherapy sensitization;

D O I：

10.1038/sj.neo.7900175

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Checkpoint kinase 1 (Chk1) is a checkpoint gene that is activated after DNA damage. It phosphorylates and inactivates the Cdc2 activating phosphatase Cdc25C. This in turn inactivates Cdc2, which leads to G2/M arrest. We report that blocking Chk1 expression by antisense or ribozymes in mammalian cells induces apoptosis and interferes with the G2/M arrest induced by adriamycin. The Chk1 inhibitor UCN-01 also blocks the G2 arrest after DNA damage and renders cells more susceptible to adriamycin. These results indicate that Chk1 is an essential gene for the checkpoint mechanism during normal cell proliferation as well as in the DNA damage response.

引用

页码：411 / 419

页数：9

共 46 条

[11] Requirement for Atr in phosphorylation of Chk1 and cell cycle regulation in response to DNA replication blocks and UV-damaged DNA in Xenopus egg extracts [J].