PMID- 24002888
OWN - NLM
STAT- MEDLINE
DCOM- 20151201
LR  - 20220311
IS  - 1868-6982 (Electronic)
IS  - 1868-6974 (Linking)
VI  - 21
IP  - 4
DP  - 2014 Apr
TI  - Mammalian target of rapamycin signaling activation patterns in pancreatic 
      neuroendocrine tumors.
PG  - 288-95
LID - 10.1002/jhbp.26 [doi]
AB  - BACKGROUND: Phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin 
      (mTOR) pathway dysregulation has been implicated in the development of various 
      human cancers. However, expression of mTOR cascade components in pancreatic 
      neuroendocrine tumors (PNETs) has not been fully explored. The aim of this study 
      was to assess the expression of mTOR pathway in PNETs using immunohistochemistry. 
      METHODS: From December 1984 to April 2012, we surgically treated 42 patients with 
      PNETs. We used immunohistochemistry to evaluate expression of mTOR, 
      phosphorylated mTOR (p-mTOR), p70S6 kinase (S6K), phosphorylated S6 ribosomal 
      protein (p-S6rp), eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), and 
      phosphorylated 4E-BP1 (p-4E-BP1) in the resected specimens. The relation between 
      the expression of these molecules and clinicopathological characteristics was 
      investigated. RESULTS: We identified the expression of mTOR (28.6%), p-mTOR 
      (52.4%), S6K (52.4%), p-S6rp (40.5%), 4E-BP1 (81.0%), and p-4E-BP1 (26.2%) in 
      PNETs. The expression of mTOR, p-mTOR, S6K, and p-S6rp was significantly 
      associated with tumor invasion, proliferation, and an advanced-stage. 
      Particularly, the expression of p-mTOR was related to clinically relevant factors 
      such as tumor size, vascular invasion, extrapancreatic invasion, lymph node 
      and/or distant metastasis, mitotic count, and European Neuroendocrine Tumor 
      Society TNM staging as well as the 2004 and 2010 World Health Organization (WHO) 
      classification. In addition, p-S6rp expression was related to vascular invasion, 
      extrapancreatic invasion, lymph node and distant metastasis, mitotic count, and 
      the 2010 WHO classification. In contrast, no significant relation between 4E-BP1 
      activation and clinicopathological factors was observed. The expression of p-mTOR 
      was strongly correlated with that of p-S6rp (r = 0.474, P = 0.002). CONCLUSIONS: 
      Our results suggest that activation of the mTOR/S6K signaling pathway plays a 
      significant role in tumorigenesis and progression of PNET.
CI  - (c) 2013 Japanese Society of Hepato-Biliary-Pancreatic Surgery.
FAU - Komori, Yoko
AU  - Komori Y
AD  - Department 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.
FAU - Yada, Kazuhiro
AU  - Yada K
FAU - Ohta, Masayuki
AU  - Ohta M
FAU - Uchida, Hiroki
AU  - Uchida H
FAU - Iwashita, Yukio
AU  - Iwashita Y
FAU - Fukuzawa, Kengo
AU  - Fukuzawa K
FAU - Kashima, Kenji
AU  - Kashima K
FAU - Yokoyama, Shigeo
AU  - Yokoyama S
FAU - Inomata, Masafumi
AU  - Inomata M
FAU - Kitano, Seigo
AU  - Kitano S
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
DEP - 20130903
PL  - Japan
TA  - J Hepatobiliary Pancreat Sci
JT  - Journal of hepato-biliary-pancreatic sciences
JID - 101528587
RN  - 0 (DNA, Neoplasm)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - DNA, Neoplasm/*genetics
MH  - Disease Progression
MH  - Female
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Immunohistochemistry
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Middle Aged
MH  - Neuroendocrine Tumors/diagnosis/*genetics/metabolism
MH  - Pancreatic Neoplasms/diagnosis/*genetics/metabolism
MH  - Prognosis
MH  - Retrospective Studies
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/biosynthesis/*genetics
MH  - Tomography, X-Ray Computed
MH  - Young Adult
OTO - NOTNLM
OT  - Immunohistochemistry
OT  - Mammalian target of rapamycin inhibitor
OT  - Mammalian target of rapamycin signaling pathway
OT  - Pancreatic neuroendocrine tumors
EDAT- 2013/09/05 06:00
MHDA- 2015/12/15 06:00
CRDT- 2013/09/05 06:00
PHST- 2013/09/05 06:00 [entrez]
PHST- 2013/09/05 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
AID - 10.1002/jhbp.26 [doi]
PST - ppublish
SO  - J Hepatobiliary Pancreat Sci. 2014 Apr;21(4):288-95. doi: 10.1002/jhbp.26. Epub 
      2013 Sep 3.