PMID- 12208897
OWN - NLM
STAT- MEDLINE
DCOM- 20020930
LR  - 20211203
IS  - 0027-8874 (Print)
IS  - 0027-8874 (Linking)
VI  - 94
IP  - 17
DP  - 2002 Sep 4
TI  - Amplification/overexpression of a mitotic kinase gene in human bladder cancer.
PG  - 1320-9
AB  - BACKGROUND: The mitotic kinase-encoding gene STK15/BTAK/ AuroraA is associated 
      with aneuploidy and transformation when overexpressed in mammalian cells. STK15 
      overexpression activates an unknown oncogenic pathway that involves centrosome 
      amplification and results in missegregation of chromosomes. Because clinical 
      prognosis and tumor aneuploidy are tightly linked in human bladder cancer, we 
      examined whether increased STK15 copy number and protein levels are linked to 
      aneuploidy in bladder cancers. METHODS: STK15 protein was visualized by 
      immunohistochemistry in 205 formalin-fixed, paraffin-embedded human bladder 
      tumors. STK15 gene copy number was evaluated in 61 tumors by Southern blot 
      hybridization and in 21 of these 61 tumors by fluorescence in situ hybridization 
      (FISH). Copy numbers of chromosomes 3, 17, 20, and 21 were evaluated by FISH with 
      chromosome-specific probes. STK15 expression levels were related to histologic 
      grade, stage, and DNA ploidy of the tumors and to the patients' follow-up data. 
      The chi-square test for association was used to analyze the relationship between 
      STK15 expression and pathologic features. All statistical tests were two-sided. 
      RESULTS: Tumors with low levels of STK15 amplification (3-4 copies) showed 
      minimal deviation in their chromosome copy number and diploid or near-diploid 
      total nuclear DNA content. Tumors with higher levels of STK15 amplification (>4 
      copies) had a major increase of chromosome copy number and of their total nuclear 
      DNA content, i.e., exhibited pronounced aneuploidy. Elevated expression of STK15 
      was strongly associated with parameters of clinical aggressiveness including high 
      histologic grade (P<.001), invasion (P<.001), increased rate of metastasis 
      (P<.001), and decreased metastasis-free (P<.001) and overall (P<.001) survival of 
      patients with bladder cancer. CONCLUSION: STK15 gene amplification and associated 
      increased expression of the mitotic kinase it encodes are associated with 
      aneuploidy and aggressive clinical behavior in human bladder cancer.
FAU - Sen, Subrata
AU  - Sen S
AD  - Division of Pathology and Laboratory Medicine, The University of Texas M. D. 
      Anderson Cancer Center, Houston 77030, USA.
FAU - Zhou, Hongyi
AU  - Zhou H
FAU - Zhang, Ruo-Dan
AU  - Zhang RD
FAU - Yoon, Dong S
AU  - Yoon DS
FAU - Vakar-Lopez, Funda
AU  - Vakar-Lopez F
FAU - Ito, Shigemi
AU  - Ito S
FAU - Jiang, Feng
AU  - Jiang F
FAU - Johnston, Dennis
AU  - Johnston D
FAU - Grossman, H Barton
AU  - Grossman HB
FAU - Ruifrok, Arnout C
AU  - Ruifrok AC
FAU - Katz, Ruth L
AU  - Katz RL
FAU - Brinkley, William
AU  - Brinkley W
FAU - Czerniak, Bogdan
AU  - Czerniak B
LA  - eng
GR  - R01CA41424/CA/NCI NIH HHS/United States
GR  - R01CA61979/CA/NCI NIH HHS/United States
GR  - R01CA66723/CA/NCI NIH HHS/United States
GR  - R01CA89716/CA/NCI NIH HHS/United States
GR  - U01CA85078/CA/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Natl Cancer Inst
JT  - Journal of the National Cancer Institute
JID - 7503089
RN  - EC 2.7.11.1 (AURKA protein, human)
RN  - EC 2.7.11.1 (Aurora Kinase A)
RN  - EC 2.7.11.1 (Aurora Kinases)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Aneuploidy
MH  - Aurora Kinase A
MH  - Aurora Kinases
MH  - Blotting, Southern
MH  - Blotting, Western
MH  - Female
MH  - Gene Amplification
MH  - Gene Dosage
MH  - Gene Expression
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Middle Aged
MH  - Protein Serine-Threonine Kinases/*genetics/*metabolism
MH  - Retrospective Studies
MH  - Tumor Cells, Cultured
MH  - Urinary Bladder Neoplasms/*enzymology/*genetics/pathology
EDAT- 2002/09/05 10:00
MHDA- 2002/10/02 04:00
CRDT- 2002/09/05 10:00
PHST- 2002/09/05 10:00 [pubmed]
PHST- 2002/10/02 04:00 [medline]
PHST- 2002/09/05 10:00 [entrez]
AID - 10.1093/jnci/94.17.1320 [doi]
PST - ppublish
SO  - J Natl Cancer Inst. 2002 Sep 4;94(17):1320-9. doi: 10.1093/jnci/94.17.1320.