Association of centrosomal kinase STK15/BTAK mRNA expression with chromosomal instability in human breast cancers.
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.
Miyoshi
Y
Y
Department of Surgical Oncology, Osaka University Medical School, Osaka, Japan.
Iwao
K
K
Egawa
C
C
Noguchi
S
S
D064096:Aurora Kinase A; D064127:Aurora Kinases; D001940:Breast / Q000201:enzymology / Q000378:metabolism; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D018385:Centrosome / Q000201:enzymology*; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D002877:Chromosomes, Human; D005260:Female; D015870:Gene Expression; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013223:Statistics as Topic
D012333:RNA, Messenger; C576917:AURKA protein, human; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases