Association of centrosomal kinaseSTK15/BTAK mRNA expression with chromosomal instability in human breast cancers

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Abstract
Over‐expression of a centrosomal serine/threonine kinase, STK15/BTAK, induces centrosome amplification, which results in chromosomal instability (CIN) in cell culture. In the present study, we investigated the correlation of STK15/BTAK mRNA expression with CIN and various clinicopathological factors in human breast cancer. STK15/BTAK mRNA levels were quantified by real‐time PCR, and CIN values were determined by FISH analysis of chromosomes 1, 11 and 17 using centromeric probes. STK15/BTAK mRNA levels (0.310 ± 0.413, mean ± SD, n = 47) in breast cancers were significantly (p < 0.01) higher than those in normal breast tissues (0.044 ± 0.029, n = 9). Furthermore, breast cancers were divided into 3 groups (low, intermediate and high) according to STK15/BTAK mRNA expression levels. CIN values of the low‐expression group (27.9 ± 12.6%, n = 18) were significantly (p < 0.01) higher than those of normal breast tissues (9.2 ± 2.6%, n = 6), and those of the high‐expression group (38.0 ± 12.7%, n = 14) were significantly (p < 0.05) higher than those of the low‐expression group. STK15/BTAK mRNA expression showed a significant (p < 0.05) correlation with high histological grade and negativity of estrogen and progesterone receptors. Our results demonstrate that STK15/BTAK mRNA is over‐expressed in the majority of breast cancers and its over‐expression is significantly associated with CIN, implicating STK15/BTAK in carcinogenesis through induction of CIN. STK15/BTAK mRNA levels might be useful as an indicator of poor prognosis and resistance to endocrine therapy.