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Updated: May 8, 2026
Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
Insights into significant pathways and gene interaction networks underlying breast cancer cell line MCF-7 treated
Jinliang Huan1, Lishan Wang, Li Xing
1Department of General Surgery, The Eighth People's Hospital of Shanghai, Shanghai 200235, China.
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.
Insights
Estradiol (E2) regulates breast cancer cell proliferation by altering gene expression and cellular pathways. This study identifies key gene networks and signaling pathways influenced by E2 in estrogen receptor-positive breast cancer cells.
Area of Science:
- Molecular Biology
- Genomics
- Cancer Research
Background:
- Estrogens regulate breast cancer cell proliferation and phenotype.
- The precise gene networks and pathways involved are not fully understood.
Purpose of the Study:
- To identify gene networks and pathways regulated by estradiol (E2) in breast cancer cells.
- To understand the temporal effects of E2 on gene expression.
Main Methods:
- Global gene expression profiling using Affymetrix GeneChip microarrays.
- KEGG pathway enrichment, PPI network construction, module analysis, and text mining.
- Analysis of estradiol (E2) effects on estrogen receptor (ER)-positive MCF-7 human breast cancer cells at 12, 24, and 48 hours.
Main Results:
- Identified 628-880 differentially expressed genes (DEGs) regulated by E2 over time.
- Pathway analysis revealed significant changes in cancer, focal adhesion, chemokine, neuroactive ligand-receptor, cytokine-cytokine receptor, calcium signaling, actin cytoskeleton, cell adhesion, axon guidance, and ErbB signaling pathways.
- PRSS23 was consistently upregulated and central in network modules; DEGs linked to ERbB, Wnt, MAPK, and IP3 pathways.
Conclusions:
- Estradiol (E2) influences diverse gene networks and cellular pathways in breast cancer.
- These pathways include metabolic and cell regulatory processes critical for E2's effects.
