Tyrosine kinase inhibitor STI-571/Gleevec down-regulates the β-catenin signaling activity

被引:88
作者
Zhou, L
An, NL
Haydon, RC
Zhou, QX
Cheng, HW
Peng, Y
Jiang, W
Luu, HH
Vanichakarn, P
Szatkowski, JP
Park, JY
Breyer, B
He, TC
机构
[1] Univ Chicago, Med Ctr, Dept Surg, Mol Oncol Lab, Chicago, IL 60637 USA
[2] Chongqing Univ Med Sci, Dept Biochem & Mol Biol, Chongqing 400046, Peoples R China
[3] Univ Chicago, Med Ctr, Comm Canc Biol, Chicago, IL 60637 USA
[4] Univ Chicago, Comm Genet, Chicago, IL 60637 USA
关键词
cancer; beta-catenin; Gleevec; STI-571; tyrosine kinase inhibitor; Wnt signal;
D O I
10.1016/S0304-3835(03)00013-2
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
beta-Catenin is a critical transducer of the Wnt signal pathway and plays an important role in many developmental and cellular processes. Deregulation of beta-catenin signaling has been observed in a broad range of human tumors. In this report, we investigated whether tyrosine kinase inhibitor STI-571 could inhibit the beta-catenin signaling activity and hence suppress cell proliferation. Our results demonstrated that STI-571 effectively inhibited the constitutive activity of beta-catenin signaling in human colon cancer cells as well as the Wnt1-induced activation of beta-catenin signaling in HOS, HTB-94, and HEK 293 cells. Furthermore, STI-571 was shown to effectively suppress the proliferation of human colon cancer cells. Finally, we demonstrated that the Wnt1-mediated activation of a GAL4-beta-catenin heterologous transcription system was effectively inhibited by STI-571. Thus, our findings suggest that tyrosine phosphorylation may play an important role in regulating beta-catenin signaling activity, and inhibition of this signaling pathway by STI-571 may be further explored as an important target for alternative/adjuvant treatments for a broader range of human cancer. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:161 / 170
页数:10
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