Related Experiment Video
Updated: May 10, 2026
Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
Key genes for modulating information flow play a temporal role as breast tumor coexpression networks are dynamically
Nadia M Penrod1, Jason H Moore
1Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth College, HB7937 One Medical Center Dr., Lebanon, NH 03766, USA.
Background:
Genes do not act in isolation but instead as part of complex regulatory networks. To understand how breast tumors adapt to the presence of the drug letrozole, at the molecular level, it is necessary to consider how the expression levels of genes in these networks change relative to one another.
Methods:
Using transcriptomic data generated from sequential tumor biopsy samples, taken at diagnosis, following 10-14 days and following 90 days of letrozole treatment, and a pairwise partial correlation statistic, we build temporal gene coexpression networks. We characterize the structure of each network and identify genes that hold prominent positions for maintaining network integrity and controlling information-flow.
Results:
Letrozole treatment leads to extensive rewiring of the breast tumor coexpression network. Approximately 20% of gene-gene relationships are conserved over time in the presence of letrozole while 80% of relationships are condition dependent. The positions of influence within the networks are transiently held with few genes stably maintaining high centrality scores across the three time points.
Conclusions:
Genes integral for maintaining network integrity and controlling information flow are dynamically changing as the breast tumor coexpression network adapts to perturbation by the drug letrozole.
Insights
Breast tumor gene networks dynamically rewire in response to letrozole treatment. Key regulatory genes shift positions, indicating adaptation to drug perturbation at the molecular level.
Area of Science:
- Genomics
- Systems Biology
- Cancer Research
Background:
- Genes function within complex regulatory networks, not in isolation.
- Understanding molecular adaptation of breast tumors to letrozole requires analyzing gene expression changes within these networks.
Purpose of the Study:
- To investigate the dynamic changes in gene coexpression networks in breast tumors during letrozole treatment.
- To identify key genes that maintain network integrity and control information flow under drug pressure.
Main Methods:
- Transcriptomic data from sequential tumor biopsies (diagnosis, 10-14 days, 90 days of letrozole treatment).
- Construction of temporal gene coexpression networks using pairwise partial correlation.
- Network structure characterization and identification of influential genes.
Main Results:
- Letrozole treatment caused significant rewiring of the breast tumor coexpression network.
- Only 20% of gene-gene relationships remained conserved during treatment; 80% were condition-dependent.
- Genes with high centrality, crucial for network integrity, showed transient influence, rarely maintaining high scores across all time points.
Conclusions:
- Genes critical for network integrity and information flow dynamically change as breast tumors adapt to letrozole.
- The gene coexpression network exhibits substantial plasticity in response to letrozole perturbation.
Related Concept Videos
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
01:33Cancer-Critical Genes I: Proto-oncogenes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:33Cancer-Critical Genes I: Proto-oncogenes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...