國家衛生研究院 NHRI:Item 3990099045/3648
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/3648


    Title: Aurora-A overexpression in mouse liver causes p53-dependent premitotic arrest during liver regeneration
    Authors: Li, CC;Chu, HY;Yang, CW;Chou, CK;Tsai, TF
    Contributors: Division of Molecular and Genomic Medicine
    Abstract: Aurora-A, a serine-threonine kinase, is frequently overexpressed in human cancers, including hepatocellular carcinoma. To study the phenotypic effects of Aurora-A overexpression on liver regeneration and tumorigenesis, we generated transgenic mice overexpressing human Aurora-A in the liver. The overexpression of Aurora-A after hepatectomy caused an earlier entry into S phase, a sustaining of DNA synthesis, and premitotic arrest in the regenerating liver. These regenerating transgenic livers show a relative increase in binuclear hepatocytes compared with regenerating wild-type livers; in addition, multipolar segregation and trinucleation could be observed only in the transgenic hepatocytes after hepatectomy. These results together suggest that defects accumulated after first round of the hepatocyte cell cycle and that there was a failure to some degree of cytokinesis. Interestingly, the p53-dependent checkpoint was activated by these abnormalities, indicating that p53 plays a crucial role during liver regeneration. Indeed, the premitotic arrest and abnormal cell death, mainly necrosis, caused by Aurora-A overexpression were genetically rescued by p53 knockout. However, trinucleation of hepatocytes remained in the regenerating livers of the transgenic mice with a p53 knockout background, indicating that the abnormal mitotic segregation and cytokinesis failure were p53 independent. Moreover, overexpression of Aurora-A in transgenic liver led to a low incidence (3.8%) of hepatic tumor formation after a long latency period. This transgenic mouse model provides a useful system that allows the study of the physiologic effects of Aurora-A on liver regeneration and the genetic pathways of Aurora-A-mediated tumorigenesis in liver.
    Date: 2009-05
    Relation: Molecular Cancer Research. 2009 May;7(5):678-688.
    Link to: http://dx.doi.org/10.1158/1541-7786.mcr-08-0483
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1541-7786&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000266284000007
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=66349129660
    Appears in Collections:[Others] Periodical Articles

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