Fraizer Gail C, Diaz Miguel F, Lee I-Ling, Grossman H Barton, Sen Subrata
Department of Biological Science, Kent State University, Kent, OH 44242, USA.
Int J Oncol. 2004 Dec;25(6):1631-9.
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.
染色体非整倍性与浸润性膀胱癌相关，参与这些变化的基因之一是Aurora-A/STK15/BTAK，它定位于20号染色体q13区域，编码一种与中心体相关的丝氨酸/苏氨酸激酶。为了更好地理解Aurora-A/STK15表达、肿瘤非整倍性与临床预后之间的关联，我们试图确定在培养的尿路上皮细胞中Aurora-A/STK15的过表达是否会促进染色体不稳定。通过免疫荧光染色、Northern印迹和Western印迹分析，我们证实膀胱肿瘤细胞系中Aurora-A/STK15的过表达增强了染色体不稳定。此外，我们观察到一些膀胱肿瘤细胞系表达的Aurora-A/STK15比培养的正常尿路上皮细胞更多，并且在具有20号染色体扩增的永生化E7尿路上皮细胞系中Aurora-A/STK15的表达高于缺乏20号染色体扩增的E6细胞系。这些结果与我们在一些T3期浸润性膀胱肿瘤中观察到的mRNA水平高于T1期浅表肿瘤和相邻正常膀胱组织的结果一致。总体而言，我们的结果表明膀胱肿瘤细胞中Aurora-A/STK15的过表达通过促进染色体不稳定导致非整倍性，从而促进肿瘤进展。
