Activation of the mTOR pathway in primary medullary thyroid carcinoma and lymph node metastases. (Articolo in rivista)

Type

• Articolo in rivista (Classe)
• Prodotto della ricerca (Classe)

Label

• Activation of the mTOR pathway in primary medullary thyroid carcinoma and lymph node metastases. (Articolo in rivista) (literal)

Anno

• 2012-01-01T00:00:00+01:00 (literal)

Alternative label

• Tamburrino A, Molinolo AA, Salerno P, Chernock RD, Raffeld M, Xi L, Gutkind JS, Moley JF, Wells SA Jr, Santoro M. (2012)
  Activation of the mTOR pathway in primary medullary thyroid carcinoma and lymph node metastases.
  in Clinical cancer research (Print)
  (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

• Tamburrino A, Molinolo AA, Salerno P, Chernock RD, Raffeld M, Xi L, Gutkind JS, Moley JF, Wells SA Jr, Santoro M. (literal)

Rivista

• Clinical cancer research (Rivista)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

• Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA. Istituto di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, 80131 Napoli, Italy. (literal)

Titolo

• Activation of the mTOR pathway in primary medullary thyroid carcinoma and lymph node metastases. (literal)

Abstract

• PURPOSE: Understanding the molecular pathogenesis of medullary thyroid carcinoma (MTC) is prerequisite to the design of targeted therapies for patients with advanced disease. EXPERIMENTAL DESIGN: We studied by immunohistochemistry the phosphorylation status of proteins of the RAS/MEK/ERK and PI3K/AKT/mTOR pathways in 53 MTC tissues (18 hereditary, 35 sporadic), including 51 primary MTCs and 2 cases with only lymph node metastases (LNM). We also studied 21 autologous LNMs, matched to 21 primary MTCs. Staining was graded on a 0 to 4 scale (S score) based on the percentage of positive cells. We also studied the functional relevance of the mTOR pathway by measuring cell viability, motility, and tumorigenicity upon mTOR chemical blockade. RESULTS: Phosphorylation of ribosomal protein S6 (pS6), a downstream target of mTOR, was evident (S >= 1) in 49 (96%) of 51 primary MTC samples. This was associated with activation of AKT (phospho-Ser473, S > 1) in 79% of cases studied. Activation of pS6 was also observed (S >= 1) in 7 (70%) of 10 hereditary C-cell hyperplasia specimens, possibly representing an early stage of C-cell transformation. It is noteworthy that 22 (96%) of 23 LNMs had a high pS6 positivity (S >= 3), which was increased compared with autologous matched primary MTCs (P = 0.024). Chemical mTOR blockade blunted viability (P < 0.01), motility (P < 0.01), and tumorigenicity (P < 0.01) of human MTC cells. CONCLUSION: The AKT/mTOR pathway is activated in MTC, particularly, in LNMs. This pathway sustains malignant features of MTC cell models. These findings suggest that targeting mTOR might be efficacious in patients with advanced MTC. (literal)

Prodotto di

• Identificazione e caratterizzazione funzionale dei geni e delle proteine coinvolti nella tumorigenesi tiroidea (SV.P15.001.004) (Modulo)
• Istituto per l'endocrinologia e l'oncologia \"Gaetano Salvatore\" (IEOS) (Istituto)

Autore CNR

• PAOLO SALERNO (Unità di personale esterno)
• ANNA TAMBURRINO (Unità di personale esterno)
• MASSIMO SANTORO (Persona)

Incoming links:

Prodotto

• Istituto per l'endocrinologia e l'oncologia \"Gaetano Salvatore\" (IEOS) (Istituto)
• Identificazione e caratterizzazione funzionale dei geni e delle proteine coinvolti nella tumorigenesi tiroidea (SV.P15.001.004) (Modulo)

Autore CNR di

• MASSIMO SANTORO (Persona)
• ANNA TAMBURRINO (Unità di personale esterno)
• PAOLO SALERNO (Unità di personale esterno)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi

• Clinical cancer research (Rivista)