Aurora B overexpression associates with the thyroid carcinoma undifferentiated phenotype and is required for thyroid carcinoma cell proliferation
Aurora B overexpression associates with the thyroid carcinoma undifferentiated phenotype and is required for thyroid carcinoma cell proliferation
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DOI：
10.1210/jc.2004-1518
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发表时间：
2005-02-01
影响因子：
5.8
通讯作者：
Portella, G
中科院分区：
文献类型：
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作者：
Sorrentino, R;Libertini, S;Portella, G
染色体数目的改变（非整倍体）在人类肿瘤中很常见。有丝分裂调节的缺失被认为会诱发癌细胞的非整倍体，并在恶性进展过程中起到驱动作用。aurora家族基因的丝氨酸/酪氨酸蛋白激酶在关键细胞周期过程的调控中起关键作用。Aurora B通过确保姐妹染色单体的定向介导染色体分离，并在正常人二倍体成纤维细胞NHDF中过表达Aurora B诱导多核。我们分析了Aurora B在人甲状腺癌中的表达。来自不同组织型的细胞系显示出Aurora B表达的增加。档案标本免疫组化分析显示，极光B在间变性甲状腺癌中高表达；相反，在正常甲状腺组织中检测不到极光B的表达。实时荧光定量PCR分析证实了极光B在甲状腺间变性癌中的强烈表达。通过RNA干扰或使用Aurora激酶活性抑制剂诱导Aurora B表达的阻断可显著降低甲状腺间变性癌细胞的生长。
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.