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Mammalian target of rapamycin signaling activation patterns in pancreatic neuroendocrine tumors

Yoko Komori1, Kazuhiro Yada, Masayuki Ohta

  • 1Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita, 879-5593, Japan. komorin@oita-u.ac.jp.

Journal of Hepato-Biliary-Pancreatic Sciences
|September 5, 2013
PubMed
Abstract

Insights

Dysregulated phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (mTOR) signaling, specifically p-mTOR and p-S6rp, is linked to pancreatic neuroendocrine tumor (PNET) progression. This suggests mTOR/S6K pathway activation is crucial in PNET development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Dysregulation of the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (mTOR) pathway is associated with various human cancers.
  • The role of mTOR cascade components in pancreatic neuroendocrine tumors (PNETs) remains underexplored.

Purpose of the Study:

  • To investigate the expression of mTOR pathway components in PNETs.
  • To correlate mTOR pathway component expression with clinicopathological characteristics of PNETs.

Main Methods:

  • Immunohistochemistry was used to assess the expression of mTOR, p-mTOR, p70S6 kinase (S6K), phosphorylated S6 ribosomal protein (p-S6rp), 4E-binding protein 1 (4E-BP1), and phosphorylated 4E-BP1 (p-4E-BP1).
  • Expression levels were analyzed in 42 surgically treated PNET specimens.
  • Statistical analysis was performed to determine the relationship between molecular expression and clinicopathological features.

Main Results:

  • Expression of mTOR, p-mTOR, S6K, and p-S6rp was detected in PNETs.
  • p-mTOR and p-S6rp expression significantly correlated with tumor invasion, proliferation, advanced stage, tumor size, vascular invasion, metastasis, and WHO/ENETS classifications.
  • p-mTOR expression was strongly correlated with p-S6rp expression (r=0.474, P=0.002).

Conclusions:

  • Activation of the mTOR/S6K signaling pathway is implicated in the tumorigenesis and progression of PNETs.
  • Specific markers like p-mTOR and p-S6rp may serve as indicators of PNET aggressiveness and clinical outcomes.
Keywords:
ImmunohistochemistryMammalian target of rapamycin inhibitorMammalian target of rapamycin signaling pathwayPancreatic neuroendocrine tumors

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