Source:http://linkedlifedata.com/resource/pubmed/id/20838824
Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
|
pubmed:dateCreated |
2011-2-7
|
pubmed:abstractText |
Aberrant activation of phosphoinositide-3 kinase/Akt (PI3K/Akt) and mammalian target of rapamycin (mTOR) signaling is implicated in the pathogenesis of mantle cell lymphoma (MCL). We previously showed oncogenic activation of PI3K/Akt pathway in a subset of MCL patients. In this study, we investigated downstream the immunohistochemical expression of (Ser2448)pmTOR [indicative of mTOR complex 1 (mTORC1) activation status] as well as of hypoxia-inducible factor 1 alpha (HIF-1?), hypoxia-inducible factor 2 alpha (HIF-2?), p53, and p21 in the same series of MCL patients. Additionally, correlation of these proteins with activated Akt ((Ser473)pAkt) and established histological prognostic factors was examined. Thirty-five tissue samples (28 classical type and seven blastoid variant) were included. The neoplastic cells expressed (Ser2448)pmTOR in 61.7%, HIF-1? in 73.5%, HIF-2? in 23.5%, and p53 in 18.2% of patients, while p21 was negative in all examined samples. In addition, 72% of patients who expressed HIF-1? had also (Ser2448)pmTOR expression (p?=?0.041). HIF-1? expression was also correlated to an elevated (?30%) Ki-67 (p?=?0.031) and blastoid variant of disease (p?=?0.017). In conclusion, we report for the first time common expression of HIF-alphas, especially HIF-1?, in MCL patients. Furthermore, an overall activation of mTORC1?HIF-1? axis and a potential role of (Ser2448)pmTOR in the regulation of HIF-1? in MCL patients are suggested. Finally, HIF-1? appears to be associated with more aggressive disease. A pathogenetic role for both mTORC1 and HIF-1? in MCL is implied, which will possibly lead to more efficient target therapies.
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Basic Helix-Loop-Helix...,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/MTOR protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/TOR Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/endothelial PAS domain-containing...,
http://linkedlifedata.com/resource/pubmed/chemical/mTORC1 complex, human
|
pubmed:status |
MEDLINE
|
pubmed:month |
Mar
|
pubmed:issn |
1432-0584
|
pubmed:author |
pubmed-author:ArgyriouPinelopiP,
pubmed-author:BakouVassilikiV,
pubmed-author:EconomopoulosTheofanisT,
pubmed-author:EconomopoulouPanagiotaP,
pubmed-author:PanteleonVarvaraV,
pubmed-author:PapageorgiouEfstathiosE,
pubmed-author:PapageorgiouSotirios GSG,
pubmed-author:PappaVassilikiV,
pubmed-author:PsyrriAmandaA,
pubmed-author:RontogianniDimitraD,
pubmed-author:SpathisArisA
|
pubmed:issnType |
Electronic
|
pubmed:volume |
90
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
315-22
|
pubmed:meshHeading |
pubmed-meshheading:20838824-Basic Helix-Loop-Helix Transcription Factors,
pubmed-meshheading:20838824-Disease Progression,
pubmed-meshheading:20838824-Female,
pubmed-meshheading:20838824-Humans,
pubmed-meshheading:20838824-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:20838824-Immunohistochemistry,
pubmed-meshheading:20838824-Lymphoma, Mantle-Cell,
pubmed-meshheading:20838824-Male,
pubmed-meshheading:20838824-Phosphorylation,
pubmed-meshheading:20838824-Proteins,
pubmed-meshheading:20838824-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:20838824-Serine,
pubmed-meshheading:20838824-Signal Transduction,
pubmed-meshheading:20838824-TOR Serine-Threonine Kinases
|
pubmed:year |
2011
|
pubmed:articleTitle |
Hypoxia-inducible factors in mantle cell lymphoma: implication for an activated mTORC1?HIF-1? pathway.
|
pubmed:affiliation |
Department of Pathology, Evangelismos General Hospital of Athens, Athens, Greece.
|
pubmed:publicationType |
Journal Article
|