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Rapamycin treatment correlates changes in primary cilia expression with cell cycle regulation in epithelial cells

机译:雷帕霉素治疗与上皮细胞中细胞周期调节的原发性纤毛表达相关

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摘要

Primary cilia are sensory organelles that regulate cell cycle and signaling pathways. In addition to its association with cancer, dysfunction of primary cilia is responsible for the pathogenesis of polycystic kidney disease (PKD) and other ciliopathies. Because the association between cilia formation or length and cell cycle or division is poorly understood, we here evaluated their correlation in this study. Using Spectral Karyotyping (SKY) technique, we showed that PKD and the cancer/tumorigenic epithelial cells PC3, DU145, and NL20-TA were associated with abnormal ploidy. We also showed that PKD and the cancer epithelia were highly proliferative. Importantly, the cancer epithelial cells had a reduction in the presence and/or length of primary cilia relative to the normal kidney (NK) cells. We then used rapamycin to restore the expression and length of primary cilia in these cells. Our subsequent analyses indicated that both the presence and length of primary cilia were inversely correlated with cell proliferation. Collectively, our data suggest that restoring the presence and/or length of primary cilia may serve as a novel approach to inhibit cancer cell proliferation.
机译:原发性纤毛是调节细胞周期和信号通路的感觉细胞器。除了与癌症的关联外,原发性纤毛的功能障碍负责多囊肾疾病(PKD)和其他纤维病的发病机制。由于纤毛形成或长度和细胞周期或划分之间的关​​联知之甚少,我们在这里评估了本研究中的相关性。使用光谱核型化(天空)技术,我们表明PKD和癌症/致瘤上皮细胞PC3,DU145和NL20-TA与异常倍率相关。我们还表明,PKD和癌症上皮细胞增殖性高。重要的是,癌症上皮细胞相对于正常肾(NK)细胞的原发性纤毛的存在和/或长度具有降低。然后,我们使用雷帕霉素恢复这些细胞中原发性纤毛的表达和长度。我们随后的分析表明,原发性纤毛的存在和长度与细胞增殖相反。集体,我们的数据表明,恢复原发性纤毛的存在和/或长度可以作为抑制癌细胞增殖的新方法。

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