Department of General Surgery, The Eighth People's Hospital of Shanghai, Shanghai 200235, China.
Gene. 2014 Jan 1;533(1):346-55. doi: 10.1016/j.gene.2013.08.027. Epub 2013 Aug 23.
Estrogens are known to regulate the proliferation of breast cancer cells and to alter their cytoarchitectural and phenotypic properties, but the gene networks and pathways by which estrogenic hormones regulate these events are only partially understood.
We used global gene expression profiling by Affymetrix GeneChip microarray analysis, with KEGG pathway enrichment, PPI network construction, module analysis and text mining methods to identify patterns and time courses of genes that are either stimulated or inhibited by estradiol (E2) in estrogen receptor (ER)-positive MCF-7 human breast cancer cells.
Of the genes queried on the Affymetrix Human Genome U133 plus 2.0 microarray, we identified 628 (12h), 852 (24h) and 880 (48 h) differentially expressed genes (DEGs) that showed a robust pattern of regulation by E2. From pathway enrichment analysis, we found out the changes of metabolic pathways of E2 treated samples at each time point. At 12h time point, the changes of metabolic pathways were mainly focused on pathways in cancer, focal adhesion, and chemokine signaling pathway. At 24h time point, the changes were mainly enriched in neuroactive ligand-receptor interaction, cytokine-cytokine receptor interaction and calcium signaling pathway. At 48 h time point, the significant pathways were pathways in cancer, regulation of actin cytoskeleton, cell adhesion molecules (CAMs), axon guidance and ErbB signaling pathway. Of interest, our PPI network analysis and module analysis found that E2 treatment induced enhancement of PRSS23 at the three time points and PRSS23 was in the central position of each module. Text mining results showed that the important genes of DEGs have relationship with signal pathways, such as ERbB pathway (AREG), Wnt pathway (NDP), MAPK pathway (NTRK3, TH), IP3 pathway (TRA@) and some transcript factors (TCF4, MAF).
Our studies highlight the diverse gene networks and metabolic and cell regulatory pathways through which E2 operates to achieve its widespread effects on breast cancer cells.
雌激素已知可调节乳腺癌细胞的增殖，并改变其细胞结构和表型特性，但雌激素激素调节这些事件的基因网络和途径仅部分了解。
我们使用 Affymetrix GeneChip 微阵列分析进行全局基因表达谱分析，并使用 KEGG 途径富集、PPI 网络构建、模块分析和文本挖掘方法，鉴定受雌二醇（E2）刺激或抑制的基因模式和时间进程在雌激素受体（ER）阳性 MCF-7 人乳腺癌细胞中。
在 Affymetrix Human Genome U133 plus 2.0 微阵列上查询的基因中，我们鉴定了 628（12h）、852（24h）和 880（48h）个差异表达基因（DEGs），这些基因显示出 E2 强有力的调节模式。从途径富集分析中，我们发现每个时间点 E2 处理样本的代谢途径发生了变化。在 12h 时间点，代谢途径的变化主要集中在癌症、粘着斑和趋化因子信号通路。在 24h 时间点，变化主要富集在神经活性配体-受体相互作用、细胞因子-细胞因子受体相互作用和钙信号通路。在 48h 时间点，显著途径是癌症途径、肌动蛋白细胞骨架调节、细胞黏附分子（CAMs）、轴突导向和 ErbB 信号通路。有趣的是，我们的 PPI 网络分析和模块分析发现，E2 处理在三个时间点诱导 PRSS23 的增强，PRSS23 处于每个模块的中心位置。文本挖掘结果表明，DEGs 的重要基因与信号通路有关，如 ERbB 通路（AREG）、Wnt 通路（NDP）、MAPK 通路（NTRK3、TH）、IP3 通路（TRA@）和一些转录因子（TCF4、MAF）。
我们的研究强调了 E2 发挥作用以实现其对乳腺癌细胞广泛影响的不同基因网络和代谢及细胞调节途径。
