PMID- 22944293
OWN - NLM
STAT- MEDLINE
DCOM- 20130329
LR  - 20211203
IS  - 1532-8392 (Electronic)
IS  - 0046-8177 (Linking)
VI  - 44
IP  - 2
DP  - 2013 Feb
TI  - Clinicopathologic significance and function of mammalian target of rapamycin 
      activation in esophageal squamous cell carcinoma.
PG  - 226-36
LID - S0046-8177(12)00186-4 [pii]
LID - 10.1016/j.humpath.2012.05.011 [doi]
AB  - Mammalian target of rapamycin (mTOR) has emerged as a key regulator of cell 
      metabolism, growth, and proliferation. Despite the increasing significance of 
      mTOR signaling in cancer cell cycle and proliferation, the clinical significance 
      of activated mTOR in esophageal squamous cell carcinoma and its role in 
      esophageal cancer cell proliferation and invasion remain unclear. Here, we show 
      that both high levels of phosphorylated-mTOR and an increased ratio of 
      phosphorylated-mTOR/mTOR (ratio >/=0.2) were significantly associated with 
      shortened disease-specific survival in 165 patients with esophageal squamous cell 
      carcinoma in univariate analysis (P = .047 for phosphorylated-mTOR, P = .021 for 
      phosphorylated-mTOR/mTOR); phosphorylated-mTOR and phosphorylated-mTOR/mTOR 
      remained independent prognostic factors after adjusting for age, TNM stage, 
      chemotherapy, and radiation therapy in multivariate analysis (hazard ratio, 1.67, 
      P = .025 for phosphorylated-mTOR; hazard ratio, 1.95, P = .006 for 
      phosphorylated-mTOR/mTOR). Moreover, down-regulation of mTOR or mTOR complex 
      components led to attenuation of proliferation, migration, and invasion of 
      esophageal squamous cell carcinoma cell lines through suppression of cyclin D1 
      expression. Collectively, our findings suggest that phosphorylated-mTOR and the 
      ratio of phosphorylated-mTOR/mTOR are closely linked to tumor progression and 
      represent independent prognostic factors in esophageal squamous cell carcinoma, 
      thereby providing a potential therapeutic target for this malignancy.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Kim, Seok-Hyung
AU  - Kim SH
AD  - Department of Pathology, Samsung Medical Center, Sungkyunkwan University School 
      of Medicine, Seoul 135-710, Korea.
FAU - Chau, Gia Cac
AU  - Chau GC
FAU - Jang, Young Hoon
AU  - Jang YH
FAU - Lee, Seung Im
AU  - Lee SI
FAU - Pyo, Suhkneung
AU  - Pyo S
FAU - Um, Sung Hee
AU  - Um SH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120831
PL  - United States
TA  - Hum Pathol
JT  - Human pathology
JID - 9421547
RN  - 0 (Biomarkers, Tumor)
RN  - 136601-57-5 (Cyclin D1)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Biomarkers, Tumor/*metabolism
MH  - Carcinoma, Squamous Cell/*metabolism/pathology/therapy
MH  - Cell Cycle
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Child
MH  - Child, Preschool
MH  - Cyclin D1/metabolism
MH  - Disease Progression
MH  - Down-Regulation
MH  - Esophageal Neoplasms/*metabolism/pathology/therapy
MH  - Esophageal Squamous Cell Carcinoma
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Infant
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Invasiveness
MH  - Neoplasm Staging
MH  - Phosphorylation
MH  - Prognosis
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Young Adult
EDAT- 2012/09/05 06:00
MHDA- 2013/03/30 06:00
CRDT- 2012/09/05 06:00
PHST- 2012/02/08 00:00 [received]
PHST- 2012/05/13 00:00 [revised]
PHST- 2012/05/16 00:00 [accepted]
PHST- 2012/09/05 06:00 [entrez]
PHST- 2012/09/05 06:00 [pubmed]
PHST- 2013/03/30 06:00 [medline]
AID - S0046-8177(12)00186-4 [pii]
AID - 10.1016/j.humpath.2012.05.011 [doi]
PST - ppublish
SO  - Hum Pathol. 2013 Feb;44(2):226-36. doi: 10.1016/j.humpath.2012.05.011. Epub 2012 
      Aug 31.