Related Experiment Video
Updated: May 10, 2026
In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
Inhibition of tumorigenesis by the thyroid hormone receptor β in xenograft models
Won Gu Kim1, Li Zhao, Dong Wook Kim
1Laboratory of Molecular Biology, Center for Cancer Research , National Cancer Institute, Bethesda, Maryland.
Background:
Previous studies showed a close association between several types of human cancers and somatic mutations of thyroid hormone receptor β (TRβ) and reduced expression of TRβ due to epigenetic inactivation and/or deletion of the THRB gene. These observations suggest that TRβ could act as a tumor suppressor in carcinogenesis. However, the mechanisms by which TRβ could function to inhibit tumorigenesis are less well understood.
Methods:
We used the human follicular thyroid cancer cell lines (FTC-133 and FTC-236 cells) to elucidate how functional expression of the THRB gene could affect tumorigenesis. We stably expressed the THRB gene in FTC cells and evaluated the effects of the expressed TRβ on cancer cell proliferation, migration, and tumor growth in cell-based studies and xenograft models.
Results:
Expression of TRβ in FTC-133 cells, as compared with control FTC cells without TRβ, reduced cancer cell proliferation and impeded migration of tumor cells through inhibition of the AKT-mTOR-p70 S6K pathway. TRβ expression in FTC-133 and FTC-236 led to less tumor growth in xenograft models. Importantly, new vessel formation was significantly suppressed in tumors induced by FTC cells expressing TRβ compared with control FTC cells without TRβ. The decrease in vessel formation was mediated by the downregulation of vascular endothelial growth factor in FTC cells expressing TRβ.
Conclusions:
These findings indicate that TRβ acts as a tumor suppressor through downregulation of the AKT-mTOR-p70 S6K pathway and decreased vascular endothelial growth factor expression in FTC cells. The present results raise the possibility that TRβ could be considered as a potential therapeutic target for thyroid cancer.
Insights
Thyroid hormone receptor beta (TRβ) acts as a tumor suppressor by inhibiting cancer cell growth and new vessel formation. Restoring TRβ function may offer a new therapeutic strategy for thyroid cancer.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- Somatic mutations and reduced expression of thyroid hormone receptor beta (TRβ) are linked to human cancers, suggesting a tumor suppressor role.
- Mechanisms underlying TRβ's tumor-inhibitory functions remain largely unclear.
Purpose of the Study:
- To investigate the impact of functional TRβ expression on thyroid cancer progression.
- To elucidate the molecular pathways involved in TRβ-mediated tumor suppression.
Main Methods:
- Stable expression of the THRB gene in human follicular thyroid cancer (FTC) cell lines (FTC-133 and FTC-236).
- Evaluation of cancer cell proliferation, migration, and tumor growth in vitro and in vivo xenograft models.
- Analysis of the AKT-mTOR-p70 S6K pathway and vascular endothelial growth factor (VEGF) expression.
Main Results:
- TRβ expression suppressed FTC cell proliferation and migration by inhibiting the AKT-mTOR-p70 S6K pathway.
- Tumor growth was significantly reduced in xenograft models with TRβ-expressing FTC cells.
- TRβ expression decreased new vessel formation by downregulating VEGF.
Conclusions:
- TRβ functions as a tumor suppressor in follicular thyroid cancer by inhibiting the AKT-mTOR-p70 S6K pathway and reducing VEGF expression.
- TRβ represents a potential therapeutic target for thyroid cancer treatment.
Related Concept Videos
01:20Synthesis and Regulation of Thyroid Hormones
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The iodine is then...
02:38Mitogens and the Cell Cycle