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 Senba, Shinya Watanabe

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    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

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    Keywords

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

    ASJC Scopus subject areas

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

    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., Senba, 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