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Updated: Aug 17, 2026
An Orthotopic Mouse Model of Anaplastic Thyroid Carcinoma
Published on: April 17, 2013
AKT activation promotes metastasis in a mouse model of follicular thyroid carcinoma
Caroline S Kim1, Vasily V Vasko, Yasuhito Kato
1Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, 37 Convent Drive, Room 5128, Bethesda, Maryland 20892-4264, USA.
Abstract:
The phosphatidylinositol 3-kinase/AKT pathway is crucial to many cell functions, and its dysregulation in tumors is a common finding. The molecular basis of follicular thyroid cancer metastasis is not well understood but may also be influenced by AKT activation. We previously created a knockin mutant mouse that expresses a mutant thyroid hormone receptor-beta gene (TRbetaPV mouse) that spontaneously develops thyroid cancer and distant metastasis similar to human follicular thyroid cancer. In this study, we investigated whether our mouse model exhibits similar AKT activation as human follicular thyroid cancer. Western blot analysis on thyroids from both wild-type and TRbeta(PV/PV) mice revealed elevation of activated AKT in TRbeta(PV/PV) mice. Immunohistochemistry and confocal microscopy reveal activated AKT in both the thyroid and metastatic lesions of TRbeta(PV/PV) mice. Whereas all three AKT isoforms were overexpressed in primary tumors from TRbeta(PV/PV) mice in the cytoplasm of thyroid cancer cells, only AKT1 was also found in the nucleus, matching the localization of activated AKT in a pattern similar to human follicular thyroid cancer. In the metastases, all AKT isoforms correlated with phosphorylated AKT nuclear localization. We created primary thyroid cell lines derived from TRbeta(PV/PV) mice and found reduction of phosphorylated AKT levels or AKT downstream targets diminishes cell motility. Activated AKT is common to both human and mouse follicular thyroid cancer and is correlated with increased cell motility in vitro and metastasis in vivo. Thus, TRbeta(PV/PV) mice could be used to further dissect the detailed pathways underlying the progression and metastasis of follicular thyroid carcinoma.
Insights
Activated AKT signaling is common in follicular thyroid cancer and drives metastasis in both humans and TRbetaPV mice. This mouse model aids in studying cancer progression and metastasis pathways.
Area of Science:
- Oncology
- Molecular Biology
- Endocrinology
Background:
- The phosphatidylinositol 3-kinase/AKT pathway is vital for cell function and frequently dysregulated in tumors.
- Follicular thyroid cancer metastasis mechanisms are not fully understood but may involve AKT activation.
Purpose of the Study:
- To investigate AKT pathway activation in a TRbetaPV mouse model of follicular thyroid cancer.
- To compare AKT activation patterns between the mouse model and human follicular thyroid cancer.
- To assess the role of activated AKT in cancer cell motility and metastasis.
Main Methods:
- Western blot analysis of thyroid tissue from wild-type and TRbetaPV mice.
- Immunohistochemistry and confocal microscopy to localize activated AKT.
- Creation of primary thyroid cell lines from TRbetaPV mice for in vitro studies.
Main Results:
- TRbetaPV mice exhibited elevated activated AKT in thyroids compared to wild-type.
- Activated AKT was found in both primary tumors and metastatic lesions of TRbetaPV mice.
- AKT isoforms and activated AKT showed similar localization patterns in mouse and human tumors, with nuclear AKT1 observed.
- Inhibition of AKT signaling reduced cell motility in derived cell lines.
- Activated AKT correlated with increased cell motility and metastasis in vivo.
Conclusions:
- Activated AKT is a conserved feature of human and mouse follicular thyroid cancer.
- The TRbetaPV mouse model effectively recapitulates human disease features, including AKT activation and metastasis.
- Activated AKT signaling contributes to increased cell motility and metastasis in follicular thyroid cancer.
- The TRbetaPV mouse model is a valuable tool for further research into follicular thyroid carcinoma progression.
