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Aurora-A 基因在基底样乳腺癌中经常扩增。

Aurora-A gene is frequently amplified in basal-like breast cancer.

机构信息

Institute of Medical Technology, University and University Hospital of Tampere, Tampere, Finland.

出版信息

Oncol Rep. 2010 Feb;23(2):307-12.

Abstract

Aurora-A is a serine-threonine kinase having vital cellular functions in mitosis and is a promising target for therapy in treating patients with cancer. This study assesses the clinicopathological associations of AURKA gene amplification in clinical breast tumors and association of gene copy number with its mRNA and protein expression in breast cancer cell lines. In this pilot study, we examined Aurora-A gene (AURKA) amplification in 126 clinical breast tumors by chromogenic in situ hybridisation (CISH). AURKA amplification (found in 21%) showed an association with basal-like tumor phenotype (p=0.046). A separate series of basal-like breast tumors (n=26) provided further evidence of the importance of AURKA in these tumors. AURKA amplification status was associated with immunohistochemically detectable Aurora-A protein expression (p<0.0001). In breast cancer cell lines, gene amplification was strongly associated with high mRNA expression (p<0.0001). JIMT-1 cell line was found as a possible in vitro model system for testing Aurora-A inhibitors, since it has been classified as basal-like breast cancer and here it showed both AURKA gene amplification and elevated mRNA expression. AURKA gene amplification is a common genetic aberration in breast cancer, especially in tumors displaying basal-like phenotype. Thus, these patients might be suitable candidates for future targeted therapies with Aurora-A inhibitors.

摘要

极光激酶 A 是一种丝氨酸/苏氨酸激酶,在有丝分裂中具有重要的细胞功能,是治疗癌症患者的有前途的治疗靶点。本研究评估了临床乳腺癌中 AURKA 基因扩增的临床病理相关性,并评估了基因拷贝数与乳腺癌细胞系中基因 mRNA 和蛋白表达的相关性。在这项初步研究中,我们通过显色原位杂交 (CISH) 检测了 126 例临床乳腺癌中的极光激酶 A 基因 (AURKA) 扩增。AURKA 扩增(在 21%的病例中发现)与基底样肿瘤表型相关(p=0.046)。另一组基底样乳腺癌(n=26)进一步提供了 AURKA 在这些肿瘤中的重要性的证据。AURKA 扩增状态与免疫组化可检测的 Aurora-A 蛋白表达相关(p<0.0001)。在乳腺癌细胞系中,基因扩增与高 mRNA 表达强烈相关(p<0.0001)。JIMT-1 细胞系被认为是测试 Aurora-A 抑制剂的可能体外模型系统,因为它被归类为基底样乳腺癌,并且在这里它显示了 AURKA 基因扩增和升高的 mRNA 表达。AURKA 基因扩增是乳腺癌中常见的遗传异常,特别是在表现出基底样表型的肿瘤中。因此,这些患者可能是未来使用 Aurora-A 抑制剂进行靶向治疗的合适候选者。

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