PMID- 22136849
OWN - NLM
STAT- MEDLINE
DCOM- 20120206
LR  - 20211203
IS  - 1532-7361 (Electronic)
IS  - 0039-6060 (Linking)
VI  - 150
IP  - 6
DP  - 2011 Dec
TI  - Activation of mTOR signaling in medullary and aggressive papillary thyroid 
      carcinomas.
PG  - 1258-65
LID - 10.1016/j.surg.2011.09.022 [doi]
AB  - 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.
CI  - Copyright (c) 2011 Mosby, Inc. All rights reserved.
FAU - Kouvaraki, Maria A
AU  - Kouvaraki MA
AD  - Department of Surgery, University of Thessaly, University Hospital of Larissa, 
      Larissa, Greece.
FAU - Liakou, Chrysoula
AU  - Liakou C
FAU - Paraschi, Adriani
AU  - Paraschi A
FAU - Dimas, Konstantinos
AU  - Dimas K
FAU - Patsouris, Efstratios
AU  - Patsouris E
FAU - Tseleni-Balafouta, Sofia
AU  - Tseleni-Balafouta S
FAU - Rassidakis, George Z
AU  - Rassidakis GZ
FAU - Moraitis, Dimitrios
AU  - Moraitis D
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Surgery
JT  - Surgery
JID - 0417347
RN  - 0 (Eukaryotic Initiation Factor-4E)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
RN  - Thyroid cancer, medullary
SB  - IM
MH  - Adult
MH  - Blotting, Western
MH  - Carcinoma
MH  - Carcinoma, Neuroendocrine
MH  - Carcinoma, Papillary
MH  - Cell Death/drug effects
MH  - Cell Line, Tumor
MH  - Eukaryotic Initiation Factor-4E/metabolism
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Signal Transduction/drug effects
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/*metabolism
MH  - Thyroid Cancer, Papillary
MH  - Thyroid Neoplasms/*metabolism/pathology
MH  - Tumor Cells, Cultured
EDAT- 2011/12/06 06:00
MHDA- 2012/02/07 06:00
CRDT- 2011/12/06 06:00
PHST- 2011/03/02 00:00 [received]
PHST- 2011/09/15 00:00 [accepted]
PHST- 2011/12/06 06:00 [entrez]
PHST- 2011/12/06 06:00 [pubmed]
PHST- 2012/02/07 06:00 [medline]
AID - S0039-6060(11)00536-8 [pii]
AID - 10.1016/j.surg.2011.09.022 [doi]
PST - ppublish
SO  - Surgery. 2011 Dec;150(6):1258-65. doi: 10.1016/j.surg.2011.09.022.