PMID- 28427860
OWN - NLM
STAT- MEDLINE
DCOM- 20180627
LR  - 20211204
IS  - 1873-2496 (Electronic)
IS  - 1078-1439 (Linking)
VI  - 35
IP  - 10
DP  - 2017 Oct
TI  - Differential mTOR pathway profiles in bladder cancer cell line subtypes to 
      predict sensitivity to mTOR inhibition.
PG  - 593-599
LID - S1078-1439(17)30134-5 [pii]
LID - 10.1016/j.urolonc.2017.03.025 [doi]
AB  - BACKGROUND: Molecular classification of bladder cancer has been increasingly 
      proposed as a potential tool to predict clinical outcomes and responses to 
      chemotherapy. Here we focused on mechanistic target of rapamycin (mTOR) 
      inhibition as a chemotherapeutic strategy and characterized the expression 
      profile of mTOR signaling targets in representative bladder cancer cell lines 
      from basal, luminal, and either basal/luminal ("non-type") molecular subtypes. 
      MATERIALS AND METHODS: Protein and mRNA expression of mTOR signaling components 
      from representative luminal (RT4 and RT112), basal (SCaBER and 5637), and nontype 
      (T24 and J82) bladder cancer cell line subtypes were determined by Western blot 
      and database mining analysis of the Cancer Cell Line Encyclopedia. Cell viability 
      following treatment with either, Torin-2 or KU-0063794, 2 dual mTOR complex 1/2 
      inhibitors, was determined by MTT assay. Immunoblot analysis of cells treated 
      with Torin-2 or KU-0063794 was performed to determine the effects of mTOR 
      inhibition on expression and phosphorylation status of mTOR signaling components, 
      Akt, 4E-BP1, and ribosomal protein S6. RESULTS: Molecular subtypes of bladder 
      cancer cell lines each exhibited a distinct pattern of expression of 
      mTOR-associated genes and baseline phosphorylation level of Akt and 4E-BP1. Cells 
      with low levels of Akt Ser-473 phosphorylation were more resistant to the 
      cytotoxic effects of mTOR inhibition with Torin-2, but not KU-0063794. Exposure 
      to Torin-2 and KU-0063794 both potently and rapidly inhibited phosphorylation of 
      Akt Ser-473 and Thr-308, and 4E-BP1 T37/46 in cell lines that included basal and 
      nontype subtypes. CONCLUSIONS: Differential gene expression and protein activity 
      associated with mTOR signaling is observed among bladder cancer cell lines 
      stratified into basal, luminal, and nontype subtypes. Urothelial carcinomas 
      characterized by high baseline Akt Ser-473 phosphorylation may be best suited for 
      targeted mTOR therapies.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Hau, Andrew M
AU  - Hau AM
AD  - Department of Pathology, University of California, San Diego, La Jolla, CA.
FAU - Nakasaki, Manando
AU  - Nakasaki M
AD  - Department of Pathology, University of California, San Diego, La Jolla, CA.
FAU - Nakashima, Kazufumi
AU  - Nakashima K
AD  - Department of Pathology, University of California, San Diego, La Jolla, CA.
FAU - Krish, Goutam
AU  - Krish G
AD  - Department of Pathology, University of California, San Diego, La Jolla, CA.
FAU - Hansel, Donna E
AU  - Hansel DE
AD  - Department of Pathology, University of California, San Diego, La Jolla, CA; 
      Department of Urology, University of California, San Diego, La Jolla, CA. 
      Electronic address: dhansel@ucsd.edu.
LA  - eng
PT  - Journal Article
DEP - 20170418
PL  - United States
TA  - Urol Oncol
JT  - Urologic oncology
JID - 9805460
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
CIN - Urol Oncol. 2017 Oct;35(10):600-601. PMID: 28774722
MH  - Cell Line, Tumor
MH  - Humans
MH  - TOR Serine-Threonine Kinases/*genetics/metabolism
MH  - Urinary Bladder Neoplasms/*genetics/pathology
OTO - NOTNLM
OT  - Basal
OT  - Bladder cancer
OT  - Cell lines
OT  - Luminal
OT  - mTOR
OT  - mTOR inhibitor
EDAT- 2017/04/22 06:00
MHDA- 2018/06/28 06:00
CRDT- 2017/04/22 06:00
PHST- 2017/01/18 00:00 [received]
PHST- 2017/03/21 00:00 [revised]
PHST- 2017/03/22 00:00 [accepted]
PHST- 2017/04/22 06:00 [pubmed]
PHST- 2018/06/28 06:00 [medline]
PHST- 2017/04/22 06:00 [entrez]
AID - S1078-1439(17)30134-5 [pii]
AID - 10.1016/j.urolonc.2017.03.025 [doi]
PST - ppublish
SO  - Urol Oncol. 2017 Oct;35(10):593-599. doi: 10.1016/j.urolonc.2017.03.025. Epub 
      2017 Apr 18.