A monoclonal antibody against Wnt-1 induces apoptosis in human cancer cells

被引：235

作者：

He, B ^{[1
]}

You, L ^{[1
]}

Uematsu, K ^{[1
]}

Xu, ZD ^{[1
]}

Lee, AY ^{[1
]}

Matsangou, M ^{[1
]}

McCormick, F ^{[1
]}

Jablons, DM ^{[1
]}

机构：

[1] Univ Calif San Francisco, Ctr Comprehens Canc, Dept Surg, Thorac Oncol Lab, San Francisco, CA 94115 USA

来源：

NEOPLASIA | 2004年 / 6卷 / 01期

关键词：

Wnt-1; monoclonal antibody; apoptosis; cancer; human;

D O I：

10.1016/S1476-5586(04)80048-4

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Aberrant activation of the Wingless-type (Wnt)/beta-catenin signaling pathway is associated with a variety of human cancers. Little is known regarding the role that Wnt ligands play in human carcinogenesis. To test whether a Wnt-1 signal is a survival factor in human cancer cells and thus may serve as a potential cancer therapeutic target, we investigated the effect of inhibition of Wnt-1 signaling in a variety of human cancer cell lines, including non small cell lung cancer, breast cancer, mesothelioma, and sarcoma. Both monoclonal antibody and RNA interference (RNAi) were used to inhibit Wnt-1 signaling. We found that incubation of a monoclonal anti-Wnt-1 antibody induced apoptosis and caused downstream protein changes in cancer cells overexpressing Wnt-1. In contrast, apoptosis was not detected in cells lacking or having minimal Wnt-1 expression after the antibody incubation. RNAi targeting of Wnt-1 in cancer cells overexpressing Wnt-1 demonstrated similar downstream protein changes and induction of apoptosis. The antibody also suppressed tumor growth in vivo. Our results indicate that both monoclonal anti-Wnt-1 antibody and Wnt-1 siRNA inhibit Wnt-1 signaling and can induce apoptosis in human cancer cells. These findings hold promise as a novel therapeutic strategy for cancer.

引用

页码：7 / 14

页数：8

共 26 条

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