Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation

被引:1116
作者
Zhou, HY
Kuang, J
Zhong, L
Kuo, WL
Gray, JW
Sahin, A
Brinkley, BR
Sen, S
机构
[1] Univ Texas, MD Anderson Cancer Ctr, Div Pathol & Lab Med, Houston, TX 77030 USA
[2] Univ Texas, MD Anderson Cancer Ctr, Div Med, Houston, TX 77030 USA
[3] Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA
[4] Univ Calif San Francisco, Ctr Canc, San Francisco, CA 94143 USA
关键词
D O I
10.1038/2496
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
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页码:189 / 193
页数:5
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