Jeng Yung-Ming, Peng Shian-Yang, Lin Chiao-Ying, Hsu Hey-Chi
Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan.
Clin Cancer Res. 2004 Mar 15;10(6):2065-71. doi: 10.1158/1078-0432.ccr-1057-03.
Aurora-A/STK15/BTAK, a centrosome-associated serine/threonine kinase, has been shown to induce chromosomal instability, leading to aneuploidy and cell transformation. The purpose of this study was to investigate the expression and amplification of Aurora-A in hepatocellular carcinoma (HCC).
Aurora-A mRNA levels were measured in 224 HCCs and 199 paired nontumorous liver tissues by reverse transcription-PCR. Aurora-A mRNA and protein levels of 8 were also measured by reverse transcription-PCR and Western blot hybridization in 8 liver cancer cell lines. Amplification of Aurora-A was determined by Southern blot hybridization in 99 cases.
Aurora-A was overexpressed in 137 of 224 (61%) HCCs and all 8 of the cell lines. Overexpression of Aurora-A was associated with high-grade (grade II-IV), and high-stage (stage IIIB-IV) tumors, p53 mutation, infrequent beta-catenin mutation, and poor outcome. Aurora-A overexpression and p53 mutation acted synergistically toward poor prognosis. Amplification of Aurora-A was detected only in 3 HCCs.
The results show that Aurora-A is overexpressed frequently in HCC, and correlated with high grade and high stage, indicating that overexpression of Aurora-A plays a role in the development and progression of HCC.
Aurora-A/STK15/BTAK是一种与中心体相关的丝氨酸/苏氨酸激酶，已被证明可诱导染色体不稳定性，导致非整倍体和细胞转化。本研究旨在探讨Aurora-A在肝细胞癌（HCC）中的表达及扩增情况。
采用逆转录-聚合酶链反应（RT-PCR）检测224例HCC组织及199例配对的癌旁肝组织中Aurora-A mRNA水平。同时，应用RT-PCR和蛋白质印迹杂交技术检测8种肝癌细胞系中Aurora-A mRNA和蛋白水平。采用Southern印迹杂交法检测99例样本中Aurora-A基因的扩增情况。
224例HCC组织中有137例（61%）以及所有8种细胞系中Aurora-A均呈过表达。Aurora-A过表达与高分级（Ⅱ-Ⅳ级）、高分期（ⅢB-Ⅳ期）肿瘤、p53突变、β-连环蛋白突变少见及预后不良相关。Aurora-A过表达与p53突变对预后不良起协同作用。仅在3例HCC中检测到Aurora-A基因扩增。
结果表明，Aurora-A在HCC中频繁过表达，并与高分级和高分期相关，提示Aurora-A过表达在HCC的发生发展中起作用。
