Targeting Ligand-Activated ErbB2 Signaling Inhibits Breast and Prostate Tumor Growth

Cancer Cell. 2002 Aug;2(2):127-37. doi: 10.1016/s1535-6108(02)00097-1.

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 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.

Publication types

  • Comment
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgens / metabolism
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Division / drug effects
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Ligands
  • Male
  • Mice
  • Neoplasm Transplantation
  • Neuregulin-1 / pharmacology
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Protein Binding / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptor, ErbB-2 / antagonists & inhibitors*
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / immunology
  • Receptor, ErbB-2 / metabolism
  • Receptor, ErbB-3 / metabolism
  • Signal Transduction* / drug effects
  • Time Factors
  • Transplantation, Heterologous
  • Tumor Cells, Cultured

Substances

  • Androgens
  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Ligands
  • Neuregulin-1
  • RNA, Messenger
  • Receptor, ErbB-2
  • Receptor, ErbB-3