國家衛生研究院 NHRI:Item 3990099045/2131
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    题名: Activating Met mutations produce unique tumor profiles in mice with selective duplication of the mutant allele
    作者: Graveel, C;Su, YL;Koeman, J;Wang, LM;Tessarollo, L;Fiscella, M;Birchmeier, C;Swiatek, P;Bronson, R;Woude, GV
    贡献者: Division of Molecular and Genomic Medicine
    摘要: Tyrosine kinase-activating mutations in Met have been observed in hereditary papillary renal carcinomas as well as in other cancers. These mutations have been examined in several in vitro systems, where they cause constitutive Met activation, focus formation, and cell motility, and are tumorigenic in xenografts. To study the influence of these mutations on tumorigenesis in vivo, we generated mice with targeted mutations in the murine met locus. The following five mouse lines with mutant Met were created: WT, D1226N, Y1228C, M1248T, and M1248T/L1193V. We observed that mice harboring D1226N, Y1228C, and M1248T/11193V mutations developed a high frequency of sarcomas and some lymphomas, whereas the M1248T mice developed carcinomas and lymphomas. Of considerable interest, we observed trisomy of chromosome 6 and duplication of the mutant met allele in a majority of the tumors, similar to what has been reported in patients with hereditary renal papillary carcinomas. These results demonstrate that activating Met mutations and met amplification play key roles in promoting tumorigenesis in vivo. Moreover, our findings show that different mutations in the Met kinase domain can influence the types of cancers that develop.
    关键词: Multidisciplinary Sciences
    日期: 2004-12-07
    關聯: Proceedings of the National Academy of Sciences of the United States of America. 2004 Dec;101(49):17198-17203.
    Link to: http://dx.doi.org/10.1073/pnas.0407651101
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0027-8424&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000225740100040
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=10344220547
    显示于类别:[王玲美(2004-2008)] 期刊論文

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