PMID- 22789858
OWN - NLM
STAT- MEDLINE
DCOM- 20130426
LR  - 20211203
IS  - 1532-3129 (Electronic)
IS  - 0021-9975 (Linking)
VI  - 147
IP  - 4
DP  - 2012 Nov
TI  - Immunohistochemical analysis of the Akt/mTOR/4E-BP1 signalling pathway in canine 
      haemangiomas and haemangiosarcomas.
PG  - 430-40
LID - S0021-9975(12)00081-3 [pii]
LID - 10.1016/j.jcpa.2012.05.002 [doi]
AB  - The specific signalling pathways that are deregulated in canine endothelial 
      tumours have not yet fully elucidated. Therefore, the aim of the present study 
      was to examine activation of the Akt/mammalian target of rapamycin 
      (mTOR)/eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) signalling 
      pathway in spontaneously arising canine haemangiomas (HAs) and haemangiosarcomas 
      (HSAs) in order to identify novel molecular targets for treatment. 
      Surgically-resected samples of HA (n = 27), HSA (n = 37), granulation tissue (n = 
      4) and normal skin (n = 4) were investigated by immunohistochemistry. 
      Approximately 80% of the HSA samples had moderate to intense expression of 
      phosphorylated Akt at Ser473 (p-Akt Ser473), p-Akt Thr308, p-4E-BP1 Thr37/46 and 
      eukaryotic initiation factor 4E, which was significantly higher than in the HAs 
      and was similar to the expression in activated endothelial cells (ECs). Although 
      p-mTOR complex1 (p-mTORC1) Ser2448 was expressed by most of the activated ECs, 
      only 35% of the HSA samples had weak to moderate expression. Because mTORC2 and 
      phosphorylates Akt Ser473 was activated in HSA samples, the present findings 
      suggest that the mTORC2/Akt/4E-BP1 pathway, regulated independently of mTORC1, 
      may be important for targeting therapy in canine HSAs.
CI  - Copyright (c) 2012 Elsevier Ltd. All rights reserved.
FAU - Murai, A
AU  - Murai A
AD  - Laboratory of Veterinary Pathology, Department of Veterinary Medicine, Faculty of 
      Applied Biological Sciences, Gifu University, Gifu, Japan.
FAU - Abou Asa, S
AU  - Abou Asa S
FAU - Kodama, A
AU  - Kodama A
FAU - Sakai, H
AU  - Sakai H
FAU - Hirata, A
AU  - Hirata A
FAU - Yanai, T
AU  - Yanai T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120710
PL  - England
TA  - J Comp Pathol
JT  - Journal of comparative pathology
JID - 0102444
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Biomarkers, Tumor)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/*metabolism
MH  - Animals
MH  - Biomarkers, Tumor/metabolism
MH  - Dog Diseases/*metabolism/pathology
MH  - Dogs
MH  - Female
MH  - Hemangioma/metabolism/pathology/*veterinary
MH  - Hemangiosarcoma/metabolism/pathology/*veterinary
MH  - Immunohistochemistry/veterinary
MH  - Male
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Signal Transduction
MH  - Skin Neoplasms/metabolism/pathology/*veterinary
MH  - TOR Serine-Threonine Kinases/*metabolism
EDAT- 2012/07/14 06:00
MHDA- 2013/04/27 06:00
CRDT- 2012/07/14 06:00
PHST- 2012/01/05 00:00 [received]
PHST- 2012/04/10 00:00 [revised]
PHST- 2012/05/01 00:00 [accepted]
PHST- 2012/07/14 06:00 [entrez]
PHST- 2012/07/14 06:00 [pubmed]
PHST- 2013/04/27 06:00 [medline]
AID - S0021-9975(12)00081-3 [pii]
AID - 10.1016/j.jcpa.2012.05.002 [doi]
PST - ppublish
SO  - J Comp Pathol. 2012 Nov;147(4):430-40. doi: 10.1016/j.jcpa.2012.05.002. Epub 2012 
      Jul 10.