Sorrentino Rosanna, Libertini Silvana, Pallante Pier Lorenzo, Troncone Giancarlo, Palombini Lucio, Bavetsias Vassilios, Spalletti-Cernia Daniela, Laccetti Paolo, Linardopoulos Spiros, Chieffi Paolo, Fusco Alfredo, Portella Giuseppe
Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università Federico II, via S. Pansini 5, 80131 Napoli, Italy.
J Clin Endocrinol Metab. 2005 Feb;90(2):928-35. doi: 10.1210/jc.2004-1518. Epub 2004 Nov 23.
Alterations in chromosome number (aneuploidy) are common in human neoplasias. Loss of mitotic regulation is believed to induce aneuploidy in cancer cells and act as a driving force during the malignant progression. The serine/theronine protein kinases of aurora family genes play a critical role in the regulation of key cell cycle processes. Aurora B mediates chromosome segregation by ensuring orientation of sister chromatids and overexpression of Aurora B in diploid human cells NHDF (normal human diploid fibroblast) induces multinuclearity. We analyzed Aurora B expression in human thyroid carcinomas. Cell lines originating from different histotypes showed an increase in Aurora B expression. Immunohistochemical analysis of archive samples showed a high expression of Aurora B in anaplastic thyroid carcinomas; conversely, Aurora B expression was not detectable in normal thyroid tissue. Real-time PCR analysis confirmed a strong expression of Aurora B in anaplastic thyroid carcinomas. The block of Aurora B expression induced by RNA interference or by using an inhibitor of Aurora kinase activity significantly reduced the growth of thyroid anaplastic carcinoma cells.
染色体数目改变(非整倍体)在人类肿瘤中很常见。有丝分裂调控的丧失被认为会诱导癌细胞产生非整倍体,并在恶性进展过程中充当驱动力。极光激酶家族基因的丝氨酸/苏氨酸蛋白激酶在关键细胞周期进程的调控中起关键作用。极光B通过确保姐妹染色单体的定向来介导染色体分离,并且在二倍体人类细胞NHDF(正常人二倍体成纤维细胞)中极光B的过表达会诱导多核形成。我们分析了人类甲状腺癌中极光B的表达。源自不同组织类型的细胞系显示极光B表达增加。存档样本的免疫组织化学分析显示,未分化甲状腺癌中极光B表达较高;相反,在正常甲状腺组织中未检测到极光B表达。实时PCR分析证实未分化甲状腺癌中极光B有强烈表达。RNA干扰或使用极光激酶活性抑制剂诱导的极光B表达阻断显著降低了甲状腺未分化癌细胞的生长。
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