Nature Genetics
20, 189 - 193 (1998)
doi:10.1038/2496
Tumour amplified kinase STK15/BTAK induces centrosome amplification,
aneuploidy and transformationHongyi Zhou1, Jian Kuang2, Ling Zhong3, Wen-lin Kuo4, Joe Gray4, Aysegul Sahin1, Bill Brinkley3
& Subrata Sen11
Division of Pathology & Laboratory Medicine,
Houston, Texas 77030, USA. 2
Division of Medicine, University of Texas M.D. Anderson
Cancer Center, Houston, Texas 77030,
USA. 3
Department of Cell Biology, Baylor College of Medicine,
Houston, Texas 77030, USA.
4
UCSF Cancer Center, University of California,
San Francisco, California 94143, USA.
Correspondence should be addressed to Subrata Sen ssen@mdacc.tmc.edu
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
lines1 and in colon tumours2; 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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