title: Expression screening of 17q12-21 amplicon reveals GRB7 as an ERBB2-dependent oncogene.
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.
authors.affiliation: 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.
authors.forename: Makoto
authors.initials: M
authors.lastname: Saito
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kato
authors.forename: Emi
authors.initials: E
authors.lastname: Ito
authors.forename: Jiro
authors.initials: J
authors.lastname: Fujimoto
authors.forename: Kosuke
authors.initials: K
authors.lastname: Ishikawa
authors.forename: Ayano
authors.initials: A
authors.lastname: Doi
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kumazawa
authors.forename: Atsuka
authors.initials: A
authors.lastname: Matsui
authors.forename: Shiori
authors.initials: S
authors.lastname: Takebe
authors.forename: Takaomi
authors.initials: T
authors.lastname: Ishida
authors.forename: Sakura
authors.initials: S
authors.lastname: Azuma
authors.forename: Hiromi
authors.initials: H
authors.lastname: Mochizuki
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Kawamura
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yanagisawa
authors.forename: Reiko
authors.initials: R
authors.lastname: Honma
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Imai
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Ohbayashi
authors.forename: Naoki
authors.initials: N
authors.lastname: Goshima
authors.forename: Kentaro
authors.initials: K
authors.lastname: Semba
authors.forename: Shinya
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D015536:Down-Regulation; D051382:GRB7 Adaptor Protein / Q000235:genetics* / Q000378:metabolism; D005784:Gene Amplification; D006801:Humans; D051379:Mice; D016296:Mutagenesis; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D017354:Point Mutation; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011519:Proto-Oncogenes; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D015398:Signal Transduction
chemical_list: D051382:GRB7 Adaptor Protein; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D011994:Recombinant Proteins; C495955:GRB7 protein, human; C508053:ERBB2 protein, human