@article{3129210,
    title = "Activation of mTOR signaling in medullary and aggressive papillary thyroid carcinomas",
    author = "Kouvaraki, M.A. and Liakou, C. and Paraschi, A. and Dimas, K. and Patsouris, E. and Tseleni-Balafouta, S. and Rassidakis, G.Z. and Moraitis, D.",
    journal = "Gland Surgery",
    year = "2011",
    volume = "150",
    number = "6",
    pages = "1258-1265",
    doi = "10.1016/j.surg.2011.09.022",
    keywords = "initiation factor 4E;  initiation factor 4E binding protein 1;  mammalian target of rapamycin;  rapamycin, adolescent;  adult;  aged;  article;  carcinoma cell;  cell death;  cell growth;  controlled study;  disease severity;  female;  histopathology;  human;  human cell;  human tissue;  immunohistochemistry;  major clinical study;  male;  priority journal;  protein expression;  protein synthesis;  thyroid cancer;  thyroid follicular carcinoma;  thyroid medullary carcinoma;  thyroid papillary carcinoma;  tumor cell culture;  Western blotting, Adult;  Blotting, Western;  Cell Death;  Cell Line, Tumor;  Eukaryotic Initiation Factor-4E;  Female;  Humans;  Immunohistochemistry;  Male;  Middle Aged;  Neoplasm Staging;  Signal Transduction;  Sirolimus;  Thyroid Neoplasms;  TOR Serine-Threonine Kinases;  Tumor Cells, Cultured",
    abstract = "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. © 2011 Published by Mosby, Inc."
}