Expression screening of 17q12-21 amplicon reveals GRB7 as an ERBB2-dependent oncogene

FEBS Lett. 2012 Jun 12;586(12):1708-14. doi: 10.1016/j.febslet.2012.05.003. Epub 2012 May 11.


Gene amplification is a major genetic alteration in human cancers. Amplicons, amplified genomic regions, are believed to contain "driver" genes responsible for tumorigenesis. However, the significance of co-amplified genes has not been extensively studied. We have established an integrated analysis system of amplicons using retrovirus-mediated gene transfer coupled with a human full-length cDNA set. Applying this system to 17q12-21 amplicon observed in breast cancer, we identified GRB7 as a context-dependent oncogene, which modulates the ERBB2 signaling pathway through enhanced phosphorylation of ERBB2 and Akt. Our work provides an insight into the biological significance of gene amplification in human cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic / genetics*
  • Chromosomes, Human, Pair 17 / genetics*
  • Down-Regulation
  • GRB7 Adaptor Protein / genetics*
  • GRB7 Adaptor Protein / metabolism
  • Gene Amplification
  • Humans
  • Mice
  • Mutagenesis
  • NIH 3T3 Cells
  • Phosphorylation
  • Point Mutation
  • Protein Processing, Post-Translational
  • Protein Structure, Tertiary / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogenes*
  • Receptor, ErbB-2 / genetics*
  • Receptor, ErbB-2 / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Deletion
  • Signal Transduction


  • GRB7 protein, human
  • Recombinant Proteins
  • GRB7 Adaptor Protein
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Proto-Oncogene Proteins c-akt