RRC ID 43842
Author 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, Ohbayashi H, Goshima N, Semba K, Watanabe S.
Title Expression screening of 17q12-21 amplicon reveals GRB7 as an ERBB2-dependent oncogene.
Journal FEBS Lett
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.
Volume 586(12)
Pages 1708-14
Published 2012-6-12
DOI 10.1016/j.febslet.2012.05.003
PII S0014-5793(12)00360-2
PMID 22584052
MeSH Animals Cell Transformation, Neoplastic / genetics* Chromosomes, Human, Pair 17 / genetics* Down-Regulation GRB7 Adaptor Protein / genetics* GRB7 Adaptor Protein / metabolism Gene Amplification Humans Mice Mutagenesis NIH 3T3 Cells Phosphorylation Point Mutation Protein Processing, Post-Translational Protein Structure, Tertiary / genetics Proto-Oncogene Proteins c-akt / metabolism Proto-Oncogenes* Receptor, ErbB-2 / genetics* Receptor, ErbB-2 / metabolism Recombinant Proteins / genetics Recombinant Proteins / metabolism Sequence Deletion Signal Transduction
IF 2.675
Times Cited 16
Human and Animal Cells