國家衛生研究院 NHRI:Item 3990099045/8678
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    题名: SWAP-70 is required for spontaneous transformation of mouse embryo fibroblasts
    作者: Chang, YT;Shu, CL;Lai, JY;Lin, CY;Chuu, CP;Ichikawa, T;Morishita, K;Jessberger, R;Fukui, Y
    贡献者: Institute of Cellular and Systems Medicine
    摘要: Introduction: SWAP-70 is a protein that regulates F-actin rearrangement in a phosphatidylinositol 3-kinase dependent manner. It plays various roles in many cell responses. We found that some Swap-70 mutants could transform mouse fibroblasts. Mouse embryo fibroblasts (MEFs) undergo transformation after certain periods of cultivation. This may be due to mutations occurring in some of the cells. If these mutations hit sequences relevant for transformation of the cells, the cells become transformed, grow faster than other cells, and become dominant in the culture. Here we describe that SWAP-70 is required for this spontaneous transformation of MEFs. Materials and Methods: MEF1F2, a Swap-70−/− MEF line, which was cloned from primary MEFs, was used. SWAP-70 genes were introduced and expressed in these cells, and the characteristics of these cells such as cell growth, contact inhibition, and tumor formation in animals, were tested. Results and Discussion: Swap-70−/− MEFs failed to spontaneously transform for more than 5 years, suggesting that these cells were deficient in transformation. After expression of human SWAP-70, these cells underwent transformation. The phenotypes of two clones were compared. Both of them grew very rapidly and lost contact inhibition, suggesting that they were transformed. Moreover, sanguinarine, a putative SWAP-70 inhibitor reversed transforming phenotypes to normal, suggesting that SWAP-70 plays an important role for transformation of the cells. However, one clone formed tumor in nude mice but the other did not. Microarray analysis revealed that the gene expression patterns were not exactly same. These results suggest that the transformation was caused by different mutations perhaps together with transforming activity of human SWAP-70. We expressed mouse SWAP-70 in MEFs to further test whether SWAP-70 is required for transformation of MEFs. The mouse SWAP-70 gene also induced transformation of the cells. Conclusion: SWAP-70 contributes to transformation of primary cells and thus acts like an oncogene.
    日期: 2014-07
    關聯: European Journal of Cancer. 2014 Jul;50(Suppl. 5):S23.
    Link to: http://dx.doi.org/10.1016/S0959-8049(14)50088-3
    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:000351589700082
    显示于类别:[福井泰久(2010-2016)] 會議論文/會議摘要
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