國家衛生研究院 NHRI:Item 3990099045/4104
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    題名: Arecoline arrests cells at prometaphase by deregulating mitotic spindle assembly and spindle assembly checkpoint: Implication for carcinogenesis
    作者: Wang, YC;Tsai, YS;Huang, JL;Lee, KW;Kuo, CC;Wang, CS;Huang, AM;Chang, JY;Jong, YJ;Lin, CS
    貢獻者: National Institute of Cancer Research
    摘要: One apparent feature of cancerous cells is genomic instability, which may include various types of chromosomal aberrations, such as translocation, aneuploidy, and the presence of micronuclei inside the cells. Mutagenic factors that promote the emergence of genomic instability are recognized as risk factors for the development of human malignancies. In Asia, betel quid (BQ) chewing is one of such risk factors for oral cancer. Areca nut is an essential constitute of BQ and is declared as a group I carcinogen by the International Agency for Research on Cancer. However, the molecular and cellular mechanisms regarding the carcinogenicity of areca nut are not fully explored. Here we reported that arecoline, a major alkaloid of areca nut, could arrest cells at prometaphase with large amounts of misaligned chromosomes. This prometaphase arrest was evidenced by condensed chromosome pattern, increased histone H3 phosphorylation, and accumulation of mitotic proteins, including aurora A and cyclin B<sub>1</sub>. To investigate the molecular mechanisms accounting for arecoline-induced prometaphase arrest, we found that arecoline could stabilize mitotic spindle assembly, which led to distorted organization of mitotic spindles, misalignment of chromosomes, and up-regulation of spindle assembly checkpoint (SAC) genes. The SAC proteins BubR1 and Mps1 were differentially modified between the cells treated with arecoline and nocodazole. This together with aurora A overexpression suggested that SAC might be partly suppressed by arecoline. As a result, the arecoline-exposed cells might produce progeny that contained various chromosomal aberrations and exhibited genomic insta
    日期: 2010-04
    關聯: Oral Oncology. 2010 Apr;46(4):255-262.
    Link to: http://dx.doi.org/10.1016/j.oraloncology.2010.01.003
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1368-8375&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000276092200005
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=77949566843
    顯示於類別:[張俊彥] 期刊論文
    [郭靜娟] 期刊論文

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