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Expression screening of 17q12-21 amplicon reveals GRB7 as an ERBB2-dependent oncogene
Authors:Saito Makoto  Kato Yukiko  Ito Emi  Fujimoto Jiro  Ishikawa Kosuke  Doi Ayano  Kumazawa Kentaro  Matsui Atsuka  Takebe Shiori  Ishida Takaomi  Azuma Sakura  Mochizuki Hiromi  Kawamura Yoshifumi  Yanagisawa Yuka  Honma Reiko  Imai Jun-ichi  Ohbayashi Hirokazu  Goshima Naoki  Semba Kentaro  Watanabe Shinya
Institution:Department of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
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.
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