國家衛生研究院 NHRI:Item 3990099045/7052
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    题名: A new type of oncogene, SWAP-70
    作者: Fukui, Y;Shu, C
    贡献者: Institute of Cellular and Systems Medicine
    摘要: Background: SWAP-70 is a phosphatidylinositol-trisphosphate (PIP3) binding protein containing a PH domain at the central domain, an F-actin binding domain at the very carboxyl terminal domain, a coiled-coil domain at the carboxyl half, and a Rac1 domain at the amino terminal domain and has been shown to be involved in membrane ruffling induced by EGF. Material and Methods: Mutations were introduced into the SWAP-70 gene and the mutant genes were introduced normal cells and their phenotypes were observed. Results: We noticed that mouse embryo fibroblasts (MEFs) lacking SWAP 70 grow more slowly than the wild type MEFs, suggesting that SWAP-70 is regulating cell growth. We found that MEFs lacking SWAP-70 transformed by V-Src oncogene are far less aggressive than the ones bearing SWAP-70. And finally, we found that one of the SWAP-70 mutants, SWAP-70–374, can transform MEFs in vitro. The transformant survived in the medium containing low concentration of serum and made colonies in soft agar suggesting that the tranformant may be a malignant transformed cells. Therefore we surveyed the mutations in human tumors. We found that there are three tumors bearing mutations within SWAP-70 gene out of 27 samples on one of the web sites. This incidence is considerably high and implicates SWAP-70 might be related to tumors. SWAP-70 has a coiled-coil domain in the carboxyl half. SWAP-70–374’s mutation resides within this coiled-coil domain. These results suggest that the coiled-coil domain plays an important role in the regulation of cell growth. Two of the mutations found in the human tumors reside in the coiledcoil domain, which suggests that the mutations may affect the growth of the cells. We made SWAP-70 genes bearing the mutation found in the native tumors and found that introduction of these mutant genes causes morphologic transformation in normal cells. Therefore, we believe that SWAP-70 is a novel type of the oncogene. In addition to this, MEFs cultured for a long time become transformed for unknown reason. However, MEFs lacking SWAP-70 never get transformed maintaining its flat morphology and slow growth, suggesting that SWAP-70 is required for malignant tumors. These observations suggest that SWAP-70 is one of the key molecules that regulate cell growth.
    日期: 2012-07
    關聯: European Journal of Cancer. 2012 Jul;48(Suppl. 5):S32.
    Link to: http://dx.doi.org/10.1016/S0959-8049(12)70833-X
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0959-8049&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000313036500118
    显示于类别:[福井泰久(2010-2016)] 會議論文/會議摘要

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