Centrosome amplification in adult T‐cell leukemia and human T‐cell leukemia virus type 1 Tax‐induced human T cells
Centrosome amplification in adult T‐cell leukemia and human T‐cell leukemia virus type 1 Tax‐induced human T cells
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DOI：
10.1111/j.1349-7006.2006.00254.x
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发表时间：
2006-09
期刊：
影响因子：
5.7
通讯作者：
Takayuki Nitta;M. Kanai;E. Sugihara;Masakazu Tanaka;Binlian Sun;T. Nagasawa;S. Sonoda;H. Saya;M. Miwa
中科院分区：
文献类型：
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作者：
Takayuki Nitta;M. Kanai;E. Sugihara;Masakazu Tanaka;Binlian Sun;T. Nagasawa;S. Sonoda;H. Saya;M. Miwa
中心体在细胞极性、细胞周期调节和染色体分离中发挥着关键作用。最近，中心体扩增被描述为某些实体瘤和白血病非整倍性的可能原因。 ATL 是一种由 HTLV-1 引起的 T 细胞恶性肿瘤。尽管细胞转化的确切机制尚不清楚，但 HTLV-1 编码蛋白 Tax 被认为在白血病发生中发挥着至关重要的作用。在这里，我们证明从 ATL 患者中分离的淋巴细胞显示出中心体扩增，并且人类 T 细胞系在 Tax 诱导后显示出中心体扩增，而 CDK 抑制剂抑制了这种扩增。在 Tax 诱导的人类 T 细胞中，中心体扩增后也观察到微核形成。这些发现表明，Tax 解除了 CDK 活性的调节并诱导中心体扩增，这可能与 HTLV-1 的细胞转化和 HTLV-1 感染的人类 T 细胞中的染色体不稳定性有关。 （癌症科学 2006 年；97：836–841）
Centrosomes play pivotal roles in cell polarity, regulation of the cell cycle and chromosomal segregation. Centrosome amplification was recently described as a possible cause of aneuploidy in certain solid tumors and leukemias. ATL is a T‐cell malignancy caused by HTLV‐1. Although the precise mechanism of cell transformation is unclear, the HTLV‐1‐encoded protein, Tax, is thought to play a crucial role in leukemogenesis. Here we demonstrate that lymphocytes isolated from patients with ATL show centrosome amplification and that a human T cell line shows centrosome amplification after induction of Tax, which was suppressed by CDK inhibitors. Micronuclei formation was also observed after centrosome amplification in Tax‐induced human T cells. These findings suggest that Tax deregulates CDK activity and induces centrosome amplification, which might be associated with cellular transformation by HTLV‐1 and chromosomal instability in HTLV‐1‐infected human T cells. (Cancer Sci 2006; 97: 836–841)