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Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
Identification of Potential Therapeutic Genes and Pathways in Phytoestrogen Emodin Treated Breast Cancer Cell Lines
Elif Sakalli-Tecim1, Pembegul Uyar-Arpaci1, N Tulin Guray1,2
1Department of Biotechnology, Middle East Technical University, Ankara, Turkey.
Abstract:
Phytoestrogens have been investigated for their potential anti-tumorigenic effects in various cancers including breast cancer. Emodin being a phytoestrogen shows anti-carcinogenic properties especially in estrogen receptor positive (ER+) breast cancers. The aim of this study is to identify the molecular mechanism and related biological pathways in both (ER+) MCF-7 and (ER-) MDA-MB-231 breast cancer cell lines upon Emodin treatment via microarray analysis in order to find out therapeutic biomarkers. In both cell lines, first differentially expressed genes were identified, then gene ontology and functional pathway enrichment analyses were performed. Genes regulated through multiple pathways were studied together with literature and a gene cluster was determined for each cell line. Further GeneMANIA and STRING databases were used to study the interactions within the related gene clusters. The results showed that, the genes which are related to cell cycle were significantly regulated in both cell lines. Also, Forkhead Box O1-related genes were found to be prominent in MCF-7 cells. In MDA-MB-231 cells, spindle attachment checkpoint mechanism-related genes were regulated, remarkably. As a result, novel gene regulations reported in this study in response to Emodin will give more information about its metabolism and antiproliferative effect, especially in ER + cells.
Insights
Emodin, a phytoestrogen, exhibits anti-cancer properties, particularly in estrogen receptor-positive breast cancer. This study reveals Emodin
Area of Science:
- Molecular biology
- Cancer research
- Pharmacology
Background:
- Phytoestrogens, like emodin, are investigated for anti-tumorigenic effects.
- Emodin demonstrates anti-carcinogenic properties, especially in estrogen receptor-positive (ER+) breast cancers.
Purpose of the Study:
- To elucidate the molecular mechanisms of emodin in ER+ (MCF-7) and ER- (MDA-MB-231) breast cancer cells.
- To identify potential therapeutic biomarkers through microarray analysis.
Main Methods:
- Microarray analysis to identify differentially expressed genes in both cell lines.
- Gene ontology and pathway enrichment analyses.
- GeneMANIA and STRING databases for interaction analysis.
Main Results:
- Cell cycle-related genes were significantly regulated in both ER+ and ER- breast cancer cells.
- Forkhead Box O1 (FOXO1)-related genes were prominent in MCF-7 cells.
- Spindle attachment checkpoint mechanism genes were notably regulated in MDA-MB-231 cells.
Conclusions:
- Emodin treatment leads to distinct molecular pathway regulations in different breast cancer subtypes.
- Novel gene regulations identified provide insights into emodin's metabolism and antiproliferative effects, particularly in ER+ cells.
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