Sequential changes in gene expression profiles in breast cancers during treatment with the aromatase inhibitor, letrozole
Sequential changes in gene expression profiles in breast cancers during treatment with the aromatase inhibitor, letrozole
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DOI：
10.1038/tpj.2010.67
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发表时间：
2012-02-01
影响因子：
2.8
通讯作者：
Dixon, J. M.
中科院分区：
文献类型：
--
作者：
Miller, W. R.;Larionov, A.;Dixon, J. M.
该研究的目的是确定与来曲唑新辅助治疗相关的乳腺癌基因表达谱的早期（14天内）和晚期（3个月）变化。在微阵列上分析了54例患者连续肿瘤活检的RNA;通过频率，幅度和显著性分析确定变化。在3个月（1503）时发生变化的基因明显多于14天（237）。早期改变的基因与细胞周期（下调）、血管发育和细胞外基质（上调）相关;晚期改变包括“细胞代谢过程”、“前体代谢物和能量的产生”（减少）和“细胞粘附”生物粘附“（增加）。早期和晚期变化之间的显着差异是下调基因的一般位置-14天的核结构和3个月后的线粒体。这些基因表达谱的变化为了解来曲唑在乳腺癌中的分子机制提供了一个新的重要数据库。药物基因组学杂志（2012）12，10-21; doi：10.1038/tpj.2010.67; 2010年8月10日在线发表
The study aim was to identify early (within 14 days) and late changes (by 3 months) in breast cancer gene expression profiles associated with neoadjuvant therapy with letrozole. RNA from sequential tumour biopsies in 54 patients was analyzed on microarrays; changes were determined by frequency, magnitude and significance analyses. Substantially more genes were changed at 3 months (1503) than at 14 days (237). Early changed genes were associated with cell cycle (downregulation), blood vessel development and extracellular matrix (upregulation); late changes included 'cellular metabolic process', 'generation of precursor metabolites and energy' (decreased) and 'cell adhesion' biological adhesion' (increased). A striking difference between the early and late changes was the general location of downregulated genes-nuclear structures at 14 days and mitochondria after 3 months. These changes in gene expression profiles provide a new and important database by which to understand molecular mechanisms of letrozole in breast cancers. The Pharmacogenomics Journal (2012) 12, 10-21; doi:10.1038/tpj.2010.67; published online 10 August 2010