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Updated: May 11, 2026
05:39
Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Complex temporal changes in TGFβ oncogenic signaling drive thyroid carcinogenesis in a mouse model
Dong Wook Kim1, Robert L Walker, Paul S Meltzer
1Gene Regulation Section, Laboratory of Molecular Biology and.
Carcinogenesis
|May 24, 2013
Summary
Temporal gene expression changes drive thyroid cancer progression. Persistent transforming growth factor beta (TGFβ) signaling activates pathways promoting epithelial-to-mesenchymal transition, invasion, and metastasis.
Area of Science:
- Molecular Biology
- Genomics
- Cancer Research
Background:
- Understanding molecular genetic alterations in thyroid carcinogenesis is crucial.
- Dynamic temporal changes in gene expression during disease progression are not well understood.
Purpose of the Study:
- To investigate global gene expression profiles during thyroid cancer progression using a mouse model.
- To identify key molecular pathways involved in thyroid cancer development and metastasis.
Main Methods:
- Utilized complementary DNA microarrays to compare gene expression in Thrb (PV/PV) mice with wild-type mice across various time points.
- Analyzed temporal changes in gene expression patterns, including upregulated and downregulated genes.
- Applied Ingenuity Pathways Analysis to identify key signaling networks.
Main Results:
- Identified 462 upregulated and 110 downregulated genes during thyroid cancer progression.
- Discovered distinct temporal expression patterns: trending up, cyclical, and spiking for upregulated genes; trending down and cyclical for downregulated genes.
- Revealed sustained activation of the transforming growth factor beta (TGFβ)-mediated network, specifically TGFβ receptor-pSMAD2/3 signaling.
Conclusions:
- Sustained TGFβ signaling promotes epithelial-to-mesenchymal transition (EMT) by decreasing E-cadherin and increasing fibronectin, vimentin, collagens, and laminins.
- TGFβ-induced EMT facilitates cancer invasion and migration, driving metastasis.
- Complex temporal gene expression changes and persistent TGFβ signaling are key drivers of thyroid cancer progression and metastatic spread.
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