PMID- 21427787
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20110714
LR  - 20211020
IS  - 2152-7806 (Electronic)
IS  - 2229-5097 (Print)
IS  - 2152-7806 (Linking)
VI  - 2
DP  - 2011 Feb 23
TI  - mTOR inhibition reduces cellular proliferation and sensitizes pituitary adenoma 
      cells to ionizing radiation.
PG  - 22
LID - 10.4103/2152-7806.77029 [doi]
LID - 22
AB  - BACKGROUND: Pituitary adenomas are the most frequent brain tumor in adults. 
      Although histologically benign, pituitary tumors cause significant morbidity and 
      mortality. Neurosurgery and medical therapeutics may lessen the morbidity and 
      mortality associated with pituitary tumors; however, these treatments are 
      associated with significant adverse side effects. Thus, an improved understanding 
      of pituitary adenomas at the molecular and cellular level is needed to design 
      novel therapeutic compounds. METHODS: To assess the effect of mammalian target of 
      rapamycin (mTOR) inhibition on pituitary adenoma cells, rat GH3 or MMQ cells were 
      treated with the clinically useful mTOR inhibitors, rapamycin or RAD001. Cellular 
      proliferation and growth following exposure to mTOR inhibitors or radiation were 
      assessed using biochemical methods. RESULTS: In the present study, we observed 
      basal activation of mTOR, downstream of constitutive Akt signaling, in rat GH3 
      adenoma cells. Functionally, the mTOR inhibitors, rapamycin and RAD001 (500 pM-5 
      nM), induced G1 growth arrest within 24 hours, an effect associated with reduced 
      cellular proliferation. Both rapamycin and RAD001 decreased the phosphorylation 
      of mTOR at the serine 2448, a key determinant of mTOR activity. Inhibition of 
      mTOR also radiosensitized GH3 cells such that 2.5 Gy in combination with 500 pM 
      rapamycin or RAD001 reduced cellular viability more effectively than 2.5 or 10 Gy 
      alone. CONCLUSIONS: These data may support a possible therapeutic role for mTOR 
      inhibitors in limiting the cellular proliferation and radioresistance of 
      pituitary adenoma cells.
FAU - Sukumari-Ramesh, Sangeetha
AU  - Sukumari-Ramesh S
AD  - Department of Neurosurgery, Medical College of Georgia, Augusta, GA 30912, USA.
FAU - Singh, Nagendra
AU  - Singh N
FAU - Dhandapani, Krishnan M
AU  - Dhandapani KM
FAU - Vender, John R
AU  - Vender JR
LA  - eng
PT  - Journal Article
DEP - 20110223
PL  - United States
TA  - Surg Neurol Int
JT  - Surgical neurology international
JID - 101535836
PMC - PMC3050059
OTO - NOTNLM
OT  - Akt
OT  - RAD001
OT  - everolimus
OT  - mTOR
OT  - pituitary tumor
OT  - radiation
OT  - rapamycin
EDAT- 2011/03/24 06:00
MHDA- 2011/03/24 06:01
PMCR- 2011/02/23
CRDT- 2011/03/24 06:00
PHST- 2010/11/23 00:00 [received]
PHST- 2011/01/12 00:00 [accepted]
PHST- 2011/03/24 06:00 [entrez]
PHST- 2011/03/24 06:00 [pubmed]
PHST- 2011/03/24 06:01 [medline]
PHST- 2011/02/23 00:00 [pmc-release]
AID - SNI-2-22 [pii]
AID - 10.4103/2152-7806.77029 [doi]
PST - epublish
SO  - Surg Neurol Int. 2011 Feb 23;2:22. doi: 10.4103/2152-7806.77029.