Amplification/overexpression of a mitotic kinase gene in human bladder cancer
| Autor: | Hong Yi Zhou, Dong S. Yoon, Feng Jiang, H. Barton Grossman, William R. Brinkley, Ruth L. Katz, Dennis A. Johnston, Bogdan Czerniak, Shigemi Ito, Ruo Dan Zhang, Subrata Sen, Funda Vakar-Lopez, Arnout C.C. Ruifrok |
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| Rok vydání: | 2002 |
| Předmět: |
Adult
Male Cancer Research medicine.medical_specialty Blotting Western Gene Dosage Aneuploidy Gene Expression Biology Protein Serine-Threonine Kinases Gene dosage Metastasis Immunoenzyme Techniques Aurora Kinases Gene duplication medicine Tumor Cells Cultured Humans In Situ Hybridization Fluorescence Aged Aurora Kinase A Retrospective Studies Aged 80 and over Bladder cancer medicine.diagnostic_test Cytogenetics Gene Amplification Cancer Middle Aged medicine.disease Blotting Southern Oncology Urinary Bladder Neoplasms Cancer research Female Fluorescence in situ hybridization |
| Zdroj: | Journal of the National Cancer Institute. 94(17) |
| ISSN: | 0027-8874 |
| Popis: | 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 chisquare 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 |
| Databáze: | OpenAIRE |
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