Aurora-A/STK15/BTAK enhances chromosomal instability in bladder cancer cells.
Aurora-A/STK15/BTAK enhances chromosomal instability in bladder cancer cells.
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DOI：
10.3892/ijo.25.6.1631
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发表时间：
2004-12
影响因子：
5.2
通讯作者：
G. Fraizer;M. F. Diaz;I-ling Lee;H. Grossman;S. Sen
中科院分区：
文献类型：
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作者：
G. Fraizer;M. F. Diaz;I-ling Lee;H. Grossman;S. Sen
染色体非整倍体与浸润性膀胱癌相关，其中Aurora-A/STK15/BTAK基因位于染色体20q13上，编码中心体相关的丝氨酸/苏氨酸激酶。为了更好地了解Aurora-A/STK15表达、肿瘤非整倍体和临床预后之间的关系，我们试图确定Aurora-A/STK15在培养的尿路上皮细胞中过表达是否促进了染色体的不稳定性。通过免疫荧光染色、Northern和Western印迹分析，我们证实Aurora-A/STK15在膀胱癌细胞系中的过表达增强了染色体的不稳定性。此外，我们还观察到一些膀胱肿瘤细胞系比培养的正常尿路上皮细胞表达更多的Aurora-A/STK15，并且在扩增20q的永生化E7尿路上皮细胞系中Aurora-A/STK15的表达高于扩增20q的E6细胞系。这些结果与我们观察到的一些T3浸润性膀胱肿瘤中的mRNA水平高于T1浅表肿瘤和邻近的正常膀胱组织中的水平是一致的。总体而言，我们的结果表明，Aurora-A/STK15在膀胱肿瘤细胞中的过表达通过促进染色体不稳定性导致非整倍体而促进肿瘤的进展。
Chromosomal aneuploidy is associated with invasive bladder cancer and one of the genes implicated in these changes is Aurora-A/STK15/BTAK, that is localized on chromosome 20q13 and encodes a centrosome-associated serine/threonine kinase. To better understand the association between Aurora-A/STK15 expression, tumor aneuploidy and clinical prognosis, we sought to determine whether overexpression of Aurora-A/STK15 in cultured urothelial cells facilitated chromosomal instability. Using immunofluorescence staining, Northern and Western blot analyses, we verified that overexpression of Aurora-A/STK15 in bladder tumor cell lines enhanced chromosomal instability. Additionally, we observed that some bladder tumor cell lines expressed more Aurora-A/STK15 than cultured normal urothelial cells and that Aurora-A/STK15 expression was higher in an immortalized E7 urothelial cell line having 20q amplification than in an E6 line lacking 20q amplification. These results were consistent with our observations of higher mRNA levels in some T3 invasive bladder tumors than in T1 superficial tumors and adjacent normal bladder tissue. Overall our results suggest that overexpression of Aurora-A/STK15 in bladder tumor cells contributes to tumor progression by promoting chromosomal instability leading to aneuploidy.