title: Insights into significant pathways and gene interaction networks underlying breast cancer cell line MCF-7 treated with 17β-estradiol (E2).
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors: Department of General Surgery, The Eighth People's Hospital of Shanghai, Shanghai 200235, China. Electronic address: huanjl2013@126.com.
authors: Jinliang
authors: J
authors: Huan
authors: Lishan
authors: L
authors: Wang
authors: Li
authors: L
authors: Xing
authors: Xianju
authors: X
authors: Qin
authors: Lingbin
authors: L
authors: Feng
authors: Xiaofeng
authors: X
authors: Pan
authors: Ling
authors: L
authors: Zhu
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D053263:Gene Regulatory Networks / Q000187:drug effects*; D006801:Humans; D061986:MCF-7 Cells
chemical_list: D004958:Estradiol
keywords: 17β-Estradiol (E2); Breast cancer; CAMs; DAVID; DEGs; Database for Annotation, Visualization, and Integrated Discovery; EASE; ER; EREs; Expression Analysis Systematic Explore; FA; Focal adhesion; GEO; Gene; Gene Expression Omnibus; IgSF; IgSFCAMs; KEGG; Kyoto Encyclopedia of Genes and Genomes; MCAM; MCF-7; cell adhesion molecules; differentially expressed genes; estrogen receptor; estrogen responsive elements; immunoglobulin superfamily; immunoglobulin superfamily cell adhesion molecules; melanoma cell adhesion molecule