Overexpression of oncogenic STK15/BTAK/Aurora A kinase in human pancreatic cancer.
Overexpression of oncogenic STK15/BTAK/Aurora A kinase in human pancreatic cancer.
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发表时间：
2003-03
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通讯作者：
Donghui Li;Jijiang Zhu;P. Firozi;J. Abbruzzese;Douglas B. Evans;K. Cleary;H. Friess;S. Sen
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作者：
Donghui Li;Jijiang Zhu;P. Firozi;J. Abbruzzese;Douglas B. Evans;K. Cleary;H. Friess;S. Sen
目的胰腺癌中常出现包括20号染色体增加在内的多染色体异常。位于染色体20 q13上的STK 15/BTAK/Aurora A基因（编码中心体相关的丝氨酸/苏氨酸激酶）的过表达已被证明可诱导染色体不稳定性，导致多个体外实验系统中的非整倍性和细胞转化。本研究旨在探讨STK 15在胰腺癌中的表达及拷贝数的变化。实验设计在9种胰腺癌细胞系中测量STK 15在mRNA和蛋白质水平的表达以及STK 15基因的拷贝数：（a）HPAF-II;（B）Aspc-1;（c）Panc-1;（d）Panc-3;（e）Panc-28;（f）Panc-48;（g）HS 766 T;（h）MIAPaCa-2;和（i）BxPc 3。采用免疫印迹法和免疫组化法检测STK 15蛋白在正常胰腺组织和胰腺癌组织中的表达。结果STK 15在所有9个细胞系中均过表达，但基因扩增很少。原发性肿瘤组织的Western印迹分析显示，与胰腺癌患者的正常邻近组织相比，STK 15蛋白过表达2-10倍。在相同的肿瘤样本中，同时检测到STK 15相关蛋白cdc 20的过度表达和有丝分裂激活蛋白磷酸酶cdc 25的表达减少。在胰腺癌患者的38个肿瘤切片中的22个（58%）中检测到STK 15蛋白表达升高。STK 15的表达程度与肿瘤的大小、分化程度和转移状态无关。结论STK 15在胰腺肿瘤和癌细胞系中过表达，提示STK 15过表达可能在胰腺癌的发生发展中起作用。
PURPOSE Multiple chromosome abnormalities, including gain of chromosome20q, have been detected frequently in human pancreatic cancers. Overexpression of the STK15/BTAK/Aurora A gene located on chromosome 20q13, which encodes a centrosome-associated serine/threonine kinase, has been shown to induce chromosomal instability, leading to aneuploidy and cell transformation in multiple in vitro experimental systems. The purpose of this study was to investigate the expression and copy number alteration of STK15 in pancreatic cancer. EXPERIMENTAL DESIGN STK15 expression at both the mRNA and protein levels together with the copy number of STK15 gene was measured in nine pancreatic carcinoma cell lines: (a) HPAF-II; (b) Aspc-1; (c) Panc-1; (d) Panc-3; (e) Panc-28; (f) Panc-48; (g) HS766T; (h) MIAPaCa-2; and (i) BxPc3. STK15 protein expression was also examined in normal pancreatic tissues and tumors by Western blotting and immunohistochemistry. RESULTS STK15 was overexpressed in all of the nine cell lines examined, but gene amplification was infrequent. Western Blot analysis of primary tumor tissues revealed 2-10 times overexpression of STK15 protein compared with normal adjacent tissues from pancreatic cancer patients. Concurrent overexpression of cdc20, an STK15-associated protein, and reduced expression of cdc25, a mitosis-activating protein phosphatase, were detected in the same tumor samples. Elevated STK15 protein expression was detected in 22 of 38 tumor sections (58%) from pancreatic cancer patients. The extent of STK15 expression was not significantly correlated with the size, degree of differentiation, and metastasis status of the tumors. CONCLUSIONS These results show that STK15 is overexpressed in pancreatic tumors and carcinoma cell lines and suggest that overexpression of STK15 may play a role in pancreatic carcinogenesis.