1. Expression screening of 17q12-21 amplicon reveals GRB7 as an ERBB2-dependent oncogene
- Author
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Hirokazu Ohbayashi, Naoki Goshima, Hiromi Mochizuki, Jiro Fujimoto, Kosuke Ishikawa, Shinya Watanabe, Atsuka Matsui, Ayano Doi, Makoto Saito, Yoshifumi Kawamura, Sakura Azuma, Yuka Yanagisawa, Reiko Honma, Kentaro Kumazawa, Emi Ito, Kentaro Semba, Shiori Takebe, Takaomi Ishida, Yukiko Kato, and Jun-ichi Imai
- Subjects
Receptor, ErbB-2 ,Biophysics ,Down-Regulation ,medicine.disease_cause ,Biochemistry ,Mice ,Structural Biology ,Complementary DNA ,Gene duplication ,Proto-Oncogenes ,Genetics ,medicine ,Animals ,Humans ,Point Mutation ,GRB7 ,Phosphorylation ,ERBB2 ,Molecular Biology ,Gene ,Sequence Deletion ,Oncogene ,biology ,Gene Amplification ,Cell Biology ,Amplicon ,Expression screening ,Recombinant Proteins ,Protein Structure, Tertiary ,Cell Transformation, Neoplastic ,Mutagenesis ,GRB7 Adaptor Protein ,Tumorigenesis ,biology.protein ,NIH 3T3 Cells ,Signal transduction ,Carcinogenesis ,Protein Processing, Post-Translational ,Proto-Oncogene Proteins c-akt ,Chromosomes, Human, Pair 17 ,Signal Transduction - 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.
- Published
- 2012