Author/Authors :
Agus، نويسنده , , David B and Akita، نويسنده , , Robert W and Fox، نويسنده , , William D and Lewis، نويسنده , , Gail D and Higgins، نويسنده , , Brian and Pisacane، نويسنده , , Paul I and Lofgren، نويسنده , , Julie A and Tindell، نويسنده , , Charles L. Evans، نويسنده , , Douglas P and Maiese، نويسنده , , Krista and Scher، نويسنده , , Howard I and Sliwkowski، نويسنده , , Mark X، نويسنده ,
Abstract :
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 ErbB2ʹs role as a coreceptor using a monoclonal antibody, 2C4, which sterically hinders ErbB2ʹs 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.
