PMID- 24124380
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20131014
LR  - 20211021
IS  - 1178-6930 (Print)
IS  - 1178-6930 (Electronic)
IS  - 1178-6930 (Linking)
VI  - 6
DP  - 2013
TI  - AKT/mTOR substrate P70S6K is frequently phosphorylated in gallbladder cancer 
      tissue and cell lines.
PG  - 1373-84
LID - 10.2147/OTT.S46897 [doi]
AB  - BACKGROUND: Gallbladder carcinoma is a highly malignant tumor and a public health 
      problem in some parts of the world. It is characterized by a poor prognosis and 
      its resistance to radio and chemotherapy. There is an urgent need to develop 
      novel therapeutic alternatives for the treatment of gallbladder carcinoma. The 
      mammalian target of the rapamycin (mTOR) signaling pathway is activated in about 
      50% of human malignancies, and its role in gallbladder carcinoma has previously 
      been suggested. In the present study, we investigated the phosphorylation status 
      of the mTOR substrate p70S6K in preneoplastic and neoplastic gallbladder tissues 
      and evaluated the effect of three mTOR inhibitors on cell growth and migration in 
      gallbladder carcinoma cell lines. METHODS: Immunohistochemical staining of 
      phospho-p70S6K was analyzed in 181 gallbladder carcinoma cases, classified 
      according to lesion type as dysplasia, early carcinoma, or advanced carcinoma. 
      Protein expression of AKT/mTOR members was also evaluated in eight gallbladder 
      carcinoma cell lines by Western blot analysis. We selected two gallbladder 
      carcinoma cell lines (G415 and TGBC-2TKB) to evaluate the effect of rapamycin, 
      RAD001, and AZD8055 on cell viability, cell migration, and protein expression. 
      RESULTS: Our results showed that phospho-p70S6K is highly expressed in dysplasia 
      (66.7%, 12/18), early cancer (84.6%, 22/26), and advanced cancer (88.3%, 
      121/137). No statistical correlation was observed between phospho-p70S6K status 
      and any clinical or pathological features, including age, gender, ethnicity, wall 
      infiltration level, or histological differentiation (P < 0.05). In vitro 
      treatment with rapamycin, RAD001, and AZD8055 reduced cell growth, cell 
      migration, and phospho-p70S6K expression significantly in G-415 and TGBC-2TKB 
      cancer cells (P < 0.001). CONCLUSION: Our findings confirm the upregulation of 
      this signaling pathway in gallbladder carcinoma and provide a rationale for the 
      potential use of mTOR inhibitors as a therapeutic strategy for human gallbladder 
      carcinoma.
FAU - Leal, Pamela
AU  - Leal P
AD  - Department of Pathology, Universidad de La Frontera, Center of Genetical and 
      Immunological Studies-Scientific and Technological Bioresource Nucleus, Temuco, 
      Santiago, Chile.
FAU - Garcia, Patricia
AU  - Garcia P
FAU - Sandoval, Alejandra
AU  - Sandoval A
FAU - Buchegger, Kurt
AU  - Buchegger K
FAU - Weber, Helga
AU  - Weber H
FAU - Tapia, Oscar
AU  - Tapia O
FAU - Roa, Juan C
AU  - Roa JC
LA  - eng
PT  - Journal Article
DEP - 20131003
PL  - New Zealand
TA  - Onco Targets Ther
JT  - OncoTargets and therapy
JID - 101514322
PMC - PMC3794848
OTO - NOTNLM
OT  - AKT
OT  - cell line
OT  - gallbladder cancer
OT  - mTOR inhibitor
OT  - migration
OT  - p70S6K
EDAT- 2013/10/15 06:00
MHDA- 2013/10/15 06:01
PMCR- 2013/10/03
CRDT- 2013/10/15 06:00
PHST- 2013/10/15 06:00 [entrez]
PHST- 2013/10/15 06:00 [pubmed]
PHST- 2013/10/15 06:01 [medline]
PHST- 2013/10/03 00:00 [pmc-release]
AID - ott-6-1373 [pii]
AID - 10.2147/OTT.S46897 [doi]
PST - epublish
SO  - Onco Targets Ther. 2013 Oct 3;6:1373-84. doi: 10.2147/OTT.S46897. eCollection 
      2013.