Biomedical Research Institute, Shenzhen-PKU-HKUST Medical Center, Shenzhen, Guangdong Province, People's Republic of China.
Med Oncol. 2011 Dec;28(4):1017-22. doi: 10.1007/s12032-010-9602-4. Epub 2010 Jun 29.
The centrosome-associated kinase aurora A (AURKA) has been shown to be involved in genetic instability and to be over-expressed in several human carcinomas including gastric cancers (GCs). The chromosome locus of AURKA, 20q13, is frequently amplified in GCs, and the functional impact of such regions needs to be extensively investigated in large amount of clinical samples. Case-matched tissues of gastric carcinomas and adjacent normal epithelium (n=141) were included in this study. Quantitative PCR was carried out to examine the copy number and mRNA expression of AURKA in GCs. Our results showed copy-number gains of AUKRA were detected in a relative high percentage of GC samples (30.5%, 43 out of 141). There was a positive correlation between copy-number increase of AURKA and tumor progression. And copy-number gains of AURKA also showed a positive correlation with mRNA over-expression in GCs. However, expression level of AURKA mRNA was also enhanced in the group of GC samples with unaltered copy numbers. These findings indicated that sporadic gastric cancers exhibit different mechanisms of AURKA regulation and that this may impact the efficacy of aurora-targeted therapies.
中心体相关激酶 Aurora A（AURKA）已被证明参与遗传不稳定性，并在包括胃癌（GC）在内的几种人类癌中过度表达。AURKA 的染色体基因座 20q13 在 GC 中经常扩增，需要在大量临床样本中广泛研究这些区域的功能影响。本研究纳入了胃癌及其相邻正常上皮的病例匹配组织（n=141）。通过定量 PCR 检测 GC 中 AURKA 的拷贝数和 mRNA 表达。我们的结果表明，AUKRA 的拷贝数增益在相对较高比例的 GC 样本中（30.5%，43/141）被检测到。AURKA 拷贝数增加与肿瘤进展呈正相关。并且，AURKA 的拷贝数增益也与 GC 中的 mRNA 过表达呈正相关。然而，在拷贝数未改变的 GC 样本组中，AURKA mRNA 的表达水平也增强了。这些发现表明散发性胃癌表现出不同的 AURKA 调节机制，这可能影响 Aurora 靶向治疗的疗效。
