PMID- 18672974
OWN - NLM
STAT- MEDLINE
DCOM- 20081014
LR  - 20211203
IS  - 0002-9645 (Print)
IS  - 0002-9645 (Linking)
VI  - 69
IP  - 8
DP  - 2008 Aug
TI  - Evaluation of the mammalian target of rapamycin pathway and the effect of 
      rapamycin on target expression and cellular proliferation in osteosarcoma cells 
      from dogs.
PG  - 1079-84
LID - 10.2460/ajvr.69.8.1079 [doi]
AB  - OBJECTIVE: To investigate activation of the mammalian target of rapamycin (mTOR) 
      pathway and the antitumor effect of rapamycin in canine osteosarcoma cells. 
      SAMPLE POPULATION: 3 established primary canine osteosarcoma cell lines generated 
      from naturally developing tumors. PROCEDURES: Expression of total and 
      phosphorylated mTOR and p70S6 kinase was assessed by use of western blot analysis 
      in canine osteosarcoma cells with and without the addition of rapamycin. A 
      clonogenic assay was performed to determine the surviving fraction of 
      osteosarcoma cells at various concentrations of rapamycin. RESULTS: Total and 
      phosphorylated mTOR and p70S6 kinase expression was evident in all 3 cell lines 
      evaluated, which was indicative of activation of this pathway. Treatment with 
      rapamycin resulted in a time-dependent decrease in phosphorylated mTOR expression 
      and a lack of detectable phosphorylated p70S6 kinase. No detectable change in 
      expression of total mTOR and total p70S6 kinase was identified after rapamycin 
      treatment. The clonogenic assay revealed a significant dose-dependent decrease in 
      the surviving fraction for all 3 cell lines when treated with rapamycin. 
      CONCLUSIONS AND CLINICAL RELEVANCE: These data indicated that mTOR and its 
      downstream product are present and active in canine osteosarcoma cells. The 
      pathway can be inhibited by rapamycin, and treatment of cells with rapamycin 
      decreased the surviving tumor cell fraction. These data support the molecular 
      basis for further investigation into the use of mTOR inhibitors as an 
      antineoplastic approach for dogs with osteosarcoma.
FAU - Gordon, Ira K
AU  - Gordon IK
AD  - Department of Surgical and Radiological Sciences, School of Veterinary Medicine, 
      University of California, Davis, CA 95616, USA.
FAU - Ye, Fang
AU  - Ye F
FAU - Kent, Michael S
AU  - Kent MS
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Am J Vet Res
JT  - American journal of veterinary research
JID - 0375011
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Phosphoproteins)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/therapeutic use
MH  - Cell Division/drug effects
MH  - Dog Diseases/drug therapy/*metabolism
MH  - Dogs
MH  - Immunosuppressive Agents/therapeutic use
MH  - Osteosarcoma/drug therapy/*pathology
MH  - Phosphoproteins/metabolism
MH  - Phosphorylation
MH  - Protein Kinases/drug effects/*metabolism
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - Sirolimus/*therapeutic use
MH  - TOR Serine-Threonine Kinases
EDAT- 2008/08/05 09:00
MHDA- 2008/10/15 09:00
CRDT- 2008/08/05 09:00
PHST- 2008/08/05 09:00 [pubmed]
PHST- 2008/10/15 09:00 [medline]
PHST- 2008/08/05 09:00 [entrez]
AID - 10.2460/ajvr.69.8.1079 [doi]
PST - ppublish
SO  - Am J Vet Res. 2008 Aug;69(8):1079-84. doi: 10.2460/ajvr.69.8.1079.