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