Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation
Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation
复制标题
DOI：
10.1038/2496
复制
发表时间：
1998-10-01
期刊：
影响因子：
30.8
通讯作者：
Sen, S
中科院分区：
文献类型：
--
作者：
Zhou, HY;Kuang, J;Sen, S
中心体被认为通过在细胞分裂过程中建立双极纺锤体来维持基因组稳定性，确保复制的染色体平等地分离到两个子细胞。中心体复制和分布失调与染色体分离异常有关，导致许多癌细胞类型出现非整倍性。在此，我们报道 STK15（也称为 BTAK 和 aurora2）编码中心体相关激酶，在多种人类肿瘤细胞类型中扩增和过表达，并参与哺乳动物细胞中中心体复制分布异常和非整倍性的诱导。先前已在乳腺肿瘤细胞系 (1) 和结肠肿瘤 (2) 中检测到 STK15 扩增；在这里，我们报告了它在大约 12% 的原发性乳腺肿瘤以及乳腺癌、卵巢癌、结肠癌、前列腺癌、神经母细胞瘤和宫颈癌细胞系中的扩增。此外，在肿瘤细胞系中检测到 STK15 mRNA 高表达，但没有基因扩增的证据。小鼠NIH 3T3细胞中STK15的异位表达导致中心体数量异常（扩增）和体外转化的出现。最后，STK15 在近二倍体人乳腺上皮细胞中的过度表达揭示了类似的中心体异常以及非整倍体的诱导。这些发现表明 STK15 是一种关键的激酶编码基因，其过度表达会导致哺乳动物细胞中心体扩增、染色体不稳定和转化。
The centrosomes are thought to maintain genomic stability through the establishment of bipolar spindles during cell division, ensuring equal segregation of replicated chromosomes to two daughter cells. Deregulated duplication and distribution of centrosomes have been implicated in chromosome segregation abnormalities, leading to aneuploidy seen in many cancer cell types. Here, we report that STK15 (also known as BTAK and aurora2), encoding a centrosome-associated kinase, is amplified and overexpressed in multiple human tumour cell types, and is involved in the induction of centrosome duplication-distribution abnormalities and aneuploidy in mammalian cells. STK15 amplification has been previously detected in breast tumour cell lines(1) and in colon tumours(2); here, we report its amplification in approximately 12% of primary breast tumours, as well as in breast, ovarian, colon, prostate, neuroblastoma and cervical cancer cell lines. Additionally, high expression of STK15 mRNA was detected in tumour cell lines without evidence of gene amplification. Ectopic expression of STK15 in mouse NIH 3T3 cells led to the appearance of abnormal centrosome number (amplification) and transformation in vitro. Finally, overexpression of STK15 in near diploid human breast epithelial cells revealed similar centrosome abnormality, as well as induction of aneuploidy. These findings suggest that STK15 is a critical kinase-encoding gene, whose overexpression leads to centrosome amplification, chromosomal instability and transformation in mammalian cells.