Related Experiment Video
Updated: May 17, 2026
10:36
Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
A modulator based regulatory network for ERα signaling pathway.
Heng-Yi Wu1, Pengyue Zheng, Guanglong Jiang
1Center for Computational Biology and Bioinformatics, Indiana University, Indianapolis, IN, USA. hengwu@umail.iu.edu
BMC Genomics
|November 9, 2012
Summary
We developed a new method to map estrogen receptor alpha (ERα) regulatory networks. The non-genomic ERα network proved more reliable than the genomic network in breast cancer cells.
Area of Science:
- Molecular Biology
- Genomics
- Cancer Research
Background:
- Estrogen receptor alpha (ERα) critically regulates gene expression in hormone-responsive breast cancer.
- ERα mediates its effects through complex genomic and non-genomic mechanisms involving co-regulators.
- Understanding ERα's regulatory network is vital for studying breast cancer progression.
Purpose of the Study:
- To investigate the ERα regulatory network and identify novel modulators of ERα function.
- To develop and apply an analytical method for constructing ERα genomic and non-genomic regulatory networks.
- To categorize ERα/modulator/target relationships based on various functional parameters.
Main Methods:
- Proposed a linear regression model to identify translational modulators and their network relationships.
- Constructed ERα genomic and non-genomic regulatory networks using gene expression and ERα Chip-seq data from MCF-7 cells.
- Validated the networks by analyzing gene expression data from ZR-75.1 cells and comparing network overlaps.
Main Results:
- Successfully built ERα genomic and non-genomic regulatory networks by analyzing ERα/modulator/target triplets.
- The ERα non-genomic network exhibited a lower False Discovery Rate (FDR) compared to the genomic network.
- Network overlap analysis revealed a higher consistency (4%) for the non-genomic network versus the genomic network (1%) between MCF-7 and ZR-75.1 cell lines.
Conclusions:
- Introduced a novel approach to infer ERα/modulator/target relationships and construct regulatory networks.
- Demonstrated that the non-genomic regulatory network is more reliable and consistent across different breast cancer cell lines.
- The findings provide a foundation for systematic studies on ERα's role in breast cancer.
More Related Videos
09:07Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay
Published on: December 19, 2018
09:07Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation
Published on: June 21, 2016
Related Concept Videos
01:28Global Regulatory Systems
Global regulatory systems in bacteria enable rapid and coordinated responses to environmental changes by integrating sensory inputs with gene expression, ensuring efficient adaptation to fluctuating conditions. Key global regulatory mechanisms include regulons, two-component systems, sigma factors, and secondary messengers.Regulons and Global RegulatorsA regulon is a collection of genes and operons controlled by a common global regulator. These regulators enable bacteria to prioritize resource...
01:19Interactions Between Signaling Pathways
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
01:22Amplifying Signals via Enzymatic Cascade
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
02:23Master Transcription Regulators
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
02:39Positive Regulator Molecules
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
01:16Calmodulin-dependent Signaling
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...