Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation.
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 and in colon tumours; 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.
Zhou
H
H
Division of Pathology & Laboratory Medicine, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Kuang
J
J
Zhong
L
L
Kuo
W L
WL
Gray
J W
JW
Sahin
A
A
Brinkley
B R
BR
Sen
S
S
D000782:Aneuploidy; D000818:Animals; D064096:Aurora Kinase A; D064127:Aurora Kinases; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D018385:Centrosome; D019084:Fluorescent Antibody Technique, Indirect; D006367:HeLa Cells; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
C576917:AURKA protein, human; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases