TUMOR 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. Deregula ted duplication and distribution of centrosomes have been implicated i n 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 a nd 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 previo usly detected in breast tumour cell lines(1) and in colon tumours(2); here, we report its amplification in approximately 12% of primary brea st tumours, as well as in breast, ovarian, colon, prostate, neuroblast oma and cervical cancer cell lines. Additionally, high expression of S TK15 mRNA was detected in tumour cell lines without evidence of gene a mplification. Ectopic expression of STK15 in mouse NIH 3T3 cells led t o the appearance of abnormal centrosome number (amplification) and tra nsformation 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 STK1 5 is a critical kinase-encoding gene, whose overexpression leads to ce ntrosome amplification, chromosomal instability and transformation in mammalian cells.