4.5 Article

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

Journal

FEBS LETTERS
Volume 586, Issue 12, Pages 1708-1714

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2012.05.003

Keywords

Gene amplification; Expression screening; Tumorigenesis; GRB7; ERBB2

Funding

  1. JSPS KAKENHI [23241064]
  2. New Energy and Industrial Technology Development Organization (NEDO)
  3. Grants-in-Aid for Scientific Research [23241064] Funding Source: KAKEN

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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. (c) 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

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