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

Makoto Saito, Yukiko Kato, Emi Ito, Jiro Fujimoto, Kosuke Ishikawa, Ayano Doi, Kentaro Kumazawa, Atsuka Matsui, Shiori Takebe, Takaomi Ishida, Sakura Azuma, Hiromi Mochizuki, Yoshifumi Kawamura, Yuka Yanagisawa, Reiko Honma, Jun Ichi Imai, Hirokazu Ohbayashi, Naoki Goshima, Kentaro Semba, Shinya Watanabe

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1708-1714
Number of pages7
JournalFEBS Letters
Volume586
Issue number12
DOIs
Publication statusPublished - 2012 Jun 12

Keywords

  • ERBB2
  • Expression screening
  • GRB7
  • Gene amplification
  • Tumorigenesis

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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  • Cite this

    Saito, M., Kato, Y., Ito, E., Fujimoto, J., Ishikawa, K., Doi, A., Kumazawa, K., Matsui, A., Takebe, S., Ishida, T., Azuma, S., Mochizuki, H., Kawamura, Y., Yanagisawa, Y., Honma, R., Imai, J. I., Ohbayashi, H., Goshima, N., Semba, K., & Watanabe, S. (2012). Expression screening of 17q12-21 amplicon reveals GRB7 as an ERBB2-dependent oncogene. FEBS Letters, 586(12), 1708-1714. https://doi.org/10.1016/j.febslet.2012.05.003