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Updated: May 27, 2026

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
Activation of mTOR signaling in medullary and aggressive papillary thyroid carcinomas
Maria A Kouvaraki1, Chrysoula Liakou, Adriani Paraschi
1Department of Surgery, University of Thessaly, University Hospital of Larissa, Larissa, Greece.
Background:
Because mammalian target of rapamycin (mTOR) may be involved in thyroid carcinogenesis, we investigated the expression and activation patterns of mTOR signaling proteins in thyroid carcinoma cells and tumors and their association with tumor histology and aggressiveness.
Methods:
Tissue specimens from 50 patients with thyroid cancer were analyzed for eIF4E, a critical downstream target of the mTOR pathway, using immunohistochemistry. In addition, fresh-frozen samples from patients, and primary tumor cell cultures were analyzed for expression and activation of mTOR signaling proteins by Western blot. Moreover, pharmacologic studies with rapamycin were performed.
Results:
High expression of eIF4E was observed in medullary thyroid carcinomas (MTC) and in aggressive variants of papillary thyroid carcinomas (PTC) as compared with conventional PTC and follicular thyroid carcinomas (P < .0001). The level of eIF4E expression also correlated with tumor stage (P = .002). Using Western blot analysis, p-rpS6, p-4EBP1, 4EBP1, and eIF4E were detected at higher levels in aggressive PTC and MTC cells. Treatment of MTC cells with increasing concentrations of rapamycin resulted in significant cell death and in decreased cell growth associated with deactivation of the mTOR pathway.
Conclusion:
mTOR signaling, which controls protein synthesis through regulation of translation initiation, is activated in aggressive PTC and MTC and represents a promising target for investigational therapies in these patients.
Insights
Mammalian target of rapamycin (mTOR) pathway is activated in aggressive thyroid cancers. Targeting mTOR with rapamycin may offer a new therapeutic strategy for these aggressive tumors.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Mammalian target of rapamycin (mTOR) signaling is implicated in thyroid carcinogenesis.
- Investigating mTOR pathway proteins in thyroid tumors is crucial for understanding cancer progression.
Purpose of the Study:
- To examine the expression and activation of mTOR signaling proteins in thyroid carcinoma.
- To correlate mTOR pathway activity with tumor histology and aggressiveness.
Main Methods:
- Immunohistochemistry and Western blot analysis of 50 thyroid cancer specimens.
- Analysis of primary tumor cell cultures and pharmacologic studies with rapamycin.
Main Results:
- High eIF4E expression in medullary (MTC) and aggressive papillary thyroid carcinomas (PTC).
- Elevated p-rpS6, p-4EBP1, 4EBP1, and eIF4E in aggressive PTC and MTC cells.
- Rapamycin treatment reduced MTC cell growth and induced cell death.
Conclusions:
- mTOR signaling is activated in aggressive thyroid cancers (PTC and MTC).
- The mTOR pathway is a potential therapeutic target for aggressive thyroid carcinomas.
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