Related Experiment Video
Updated: Oct 19, 2025
In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
Common tumor-suppressive signaling of thyroid hormone receptor beta in breast and thyroid cancer cells
Eric L Bolf1,2, Noelle E Gillis1,2, Cole D Davidson1,2
1Department of Pharmacology, Larner College of Medicine, University of Vermont, Burlington, Vermont, USA.
Abstract:
The thyroid hormone receptor beta (TRβ) is a tumor suppressor in multiple types of solid tumors, most prominently in breast and thyroid cancer. An increased understanding of the molecular mechanisms by which TRβ abrogates tumorigenesis will aid in understanding the core tumor-suppressive functions of TRβ. Here, we restored TRβ expression in the MDA-MB-468 basal-like breast cancer cell line and perform RNA-sequencing to determine the TRβ-mediated changes in gene expression and associated signaling pathways. The TRβ expressing MDA-MB-468 cells exhibit a more epithelial character as determined by principle component analysis-based iterative PAM50 subtyping score and through reduced expression of mesenchymal cytokeratins. The epithelial to mesenchymal transition pathway is also significantly reduced. The MDA-MB-468 data set was further compared with RNA sequencing results from TRβ expressing thyroid cancer cell line SW1736 to determine which genes are TRβ correspondingly regulated across both cell types. Several pathways including lipid metabolism and chromatin remodeling processes were observed to be altered in the shared gene set. These data provide novel insights into the molecular mechanisms by which TRβ suppresses breast tumorigenesis.
Insights
Thyroid hormone receptor beta (TRβ) suppresses breast cancer by promoting an epithelial cell state and reducing mesenchymal characteristics. Restoring TRβ expression reveals key molecular pathways involved in its tumor-suppressive functions.
Area of Science:
- Molecular biology
- Cancer research
- Genomics
Background:
- Thyroid hormone receptor beta (TRβ) acts as a tumor suppressor in various cancers, including breast and thyroid malignancies.
- Understanding TRβ's molecular mechanisms is crucial for elucidating its tumor-suppressive functions and developing targeted therapies.
Purpose of the Study:
- To investigate the molecular mechanisms underlying TRβ's tumor-suppressive role in breast cancer.
- To identify TRβ-mediated gene expression changes and affected signaling pathways in breast cancer cells.
Main Methods:
- Restored TRβ expression in the MDA-MB-468 basal-like breast cancer cell line.
- Utilized RNA sequencing to analyze gene expression and pathway alterations.
- Compared gene expression data with TRβ-expressing thyroid cancer cell line (SW1736) for conserved TRβ targets.
Main Results:
- TRβ expression induced a more epithelial cell character in MDA-MB-468 cells, evidenced by PAM50 subtyping and reduced mesenchymal cytokeratins.
- Significantly reduced epithelial-to-mesenchymal transition (EMT) pathway activity was observed.
- Shared gene expression analysis across breast and thyroid cancer cell lines identified altered lipid metabolism and chromatin remodeling pathways.
Conclusions:
- TRβ restoration promotes epithelial characteristics and suppresses mesenchymal traits in breast cancer cells.
- TRβ influences key cellular processes, including lipid metabolism and chromatin remodeling, contributing to its tumor-suppressive effects.
- These findings offer novel insights into TRβ's molecular mechanisms in breast cancer suppression.
Related Concept Videos
01:15Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
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...
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:16TGF - β Signaling Pathway
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
02:38Mitogens and the Cell Cycle