mTOR inhibition reduces cellular proliferation and sensitizes pituitary adenoma cells to ionizing radiation

Hdl Handle:
http://hdl.handle.net/10675.2/640
Title:
mTOR inhibition reduces cellular proliferation and sensitizes pituitary adenoma cells to ionizing radiation
Authors:
Sukumari-Ramesh, Sangeetha; Singh, Nagendra; Dhandapani, Krishnan M.; Vender, John R.
Abstract:
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 pMâ 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.
Citation:
Surg Neurol Int. 2011 Feb 23; 2:22
Issue Date:
23-Feb-2011
URI:
http://hdl.handle.net/10675.2/640
DOI:
10.4103/2152-7806.77029
PubMed ID:
21427787
PubMed Central ID:
PMC3050059
Type:
Article
ISSN:
2152-7806
Appears in Collections:
Department of Neurosurgery: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorSukumari-Ramesh, Sangeethaen_US
dc.contributor.authorSingh, Nagendraen_US
dc.contributor.authorDhandapani, Krishnan M.en_US
dc.contributor.authorVender, John R.en_US
dc.date.accessioned2012-10-26T16:26:57Z-
dc.date.available2012-10-26T16:26:57Z-
dc.date.issued2011-02-23en_US
dc.identifier.citationSurg Neurol Int. 2011 Feb 23; 2:22en_US
dc.identifier.issn2152-7806en_US
dc.identifier.pmid21427787en_US
dc.identifier.doi10.4103/2152-7806.77029en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/640-
dc.description.abstractBackground:: 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.en_US
dc.description.abstractMethods:: 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.en_US
dc.description.abstractResults:: 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 pMâ 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.en_US
dc.description.abstractConclusions:: These data may support a possible therapeutic role for mTOR inhibitors in limiting the cellular proliferation and radioresistance of pituitary adenoma cells.en_US
dc.rights© 2011 Sukumari-Ramesh Sen_US
dc.subjectOriginal Articleen_US
dc.titlemTOR inhibition reduces cellular proliferation and sensitizes pituitary adenoma cells to ionizing radiationen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3050059en_US
dc.contributor.corporatenameDepartment of Neurosurgery-
dc.contributor.corporatenameDepartment of Biochemistry and Molecular Biology-

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