Document Detail


mTOR, S6 and AKT expression in relation to proliferation and apoptosis/autophagy in glioma.
MedLine Citation:
PMID:  19661320     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The mammalian target of rapamycin (mTOR) controls cell growth through protein synthesis regulation. It can be activated by protein kinase B (AKT) or through ribosomal S6 kinase (S6K1). In malignant glioma, mTOR inhibitors have antiproliferative and proapoptotic effects and mTOR has been suggested as a target of therapies, thus it is worthwhile to verify its relations with the phosphatidylinositol-3-kinase (PI3)/AKT cascade, proliferation and apoptosis in human gliomas.
MATERIALS AND METHODS: In a series of 64 gliomas, including high- and low-grade tumors, AKT, mTOR, S6, caspase-3, poly(ADP-ribose) polymerase 1 (PARP1) and cleaved PARP1, Ki-67/MIB.1 and beclin 1 were studied by molecular biology techniques, quantitative immunohistochemistry and Western blotting.
RESULTS: mTOR (phospho-mTOR), S6 (phospho-S6), AKT (phospho-AKT) levels and Ki-67/MIB.1 labelling index (LI) increased with increasing grade of malignancy. Epithelial growth factor receptor (EGFR) amplification correlated with EGFRwt and EGFRvIII immunohistochemistry, and with AKT expression; the latter correlated with mTOR expression, whereas S6 expression correlated with Ki-67/MIB.1 LI. Within the category of glioblastoma, S6 but not mTOR correlated with proliferation. mTOR did not show correlation with apoptosis, whereas it was inversely correlated with beclin 1, in line with the observation that autophagy is not activated in many malignancies.
CONCLUSION: The relationship of S6 with the proliferation markers emphasizes the importance of the position of S6K1 downstream AKT in the PI3/AKT pathway.
Authors:
Laura Annovazzi; Marta Mellai; Valentina Caldera; Guido Valente; Luciana Tessitore; Davide Schiffer
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anticancer research     Volume:  29     ISSN:  1791-7530     ISO Abbreviation:  Anticancer Res.     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-08-07     Completed Date:  2009-09-30     Revised Date:  2014-07-03    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  3087-94     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Apoptosis*
Apoptosis Regulatory Proteins / metabolism
Autophagy
Blotting, Western
Caspase 3 / metabolism
Cell Proliferation*
Glioma / metabolism*,  pathology*
Humans
Immunoenzyme Techniques
Ki-67 Antigen / metabolism
Membrane Proteins / metabolism
Phosphorylation
Poly(ADP-ribose) Polymerases / metabolism
Protein Kinases / metabolism*
Proto-Oncogene Proteins c-akt / metabolism*
Ribosomal Protein S6 Kinases / metabolism*
TOR Serine-Threonine Kinases
Ubiquitin-Protein Ligases / metabolism
Chemical
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/BECN1 protein, human; 0/Ki-67 Antigen; 0/Membrane Proteins; EC 2.4.2.30/PARP1 protein, human; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 2.7.-/Protein Kinases; EC 2.7.1.1/MTOR protein, human; EC 2.7.1.1/TOR Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.1/Ribosomal Protein S6 Kinases; EC 3.4.22.-/Caspase 3; EC 6.3.2.19/MIB1 ligase, human; EC 6.3.2.19/Ubiquitin-Protein Ligases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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