Targeting ligand-activated ErbB2 signaling inhibits breast and prostate tumor growth
Targeting ligand-activated ErbB2 signaling inhibits breast and prostate tumor growth
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DOI：
10.1016/s1535-6108(02)00097-1
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发表时间：
2002-08-01
期刊：
影响因子：
50.3
通讯作者：
Sliwkowski, MX
中科院分区：
文献类型：
--
作者：
Agus, DB;Akita, RW;Sliwkowski, MX
ErbB2是ErbB受体家族的无配体成员，作为EGFR、ErbB3和ErbB4的辅助受体。在这里，我们描述了一种利用单克隆抗体2C4靶向ErbB2作为辅助受体的方法，该抗体在空间上阻碍ErbB2募集到ErbB配体复合物中。在ErbB2低表达和高表达系统中，2C4均可抑制配体依赖性ErbB2信号传导。由于ErbB3受体含有一个失活的酪氨酸激酶结构域，2C4在阻断heregulin介导的ErbB3- erbb2信号传导方面非常有效。我们证明了几种乳腺和前列腺肿瘤模型的体外和体内生长受到2C4治疗的抑制。
ErbB2 is a ligand-less member of the ErbB receptor family that functions as a coreceptor with EGFR, ErbB3, and ErbB4. Here, we describe an approach to target ErbB2's role as a coreceptor using a monoclonal antibody, 2C4, which sterically hinders ErbB2's recruitment into ErbB ligand complexes. Inhibition of ligand-dependent ErbB2 signaling by 2C4 occurs in both low- and high-ErbB2-expressing systems. Since the ErbB3 receptor contains an inactive tyrosine kinase domain, 2C4 is very effective in blocking heregulin-mediated ErbB3-ErbB2 signaling. We demonstrate that the in vitro and in vivo growth of several breast and prostate tumor models is inhibited by 2C4 treatment.