Abstract:
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.
journal_name
Anticancer Resjournal_title
Anticancer researchauthors
Annovazzi L,Mellai M,Caldera V,Valente G,Tessitore L,Schiffer Dsubject
Has Abstractpub_date
2009-08-01 00:00:00pages
3087-94issue
8eissn
0250-7005issn
1791-7530pii
29/8/3087journal_volume
29pub_type
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journal_title:Anticancer research
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journal_title:Anticancer research
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journal_title:Anticancer research
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journal_title:Anticancer research
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journal_title:Anticancer research
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更新日期:2014-12-01 00:00:00
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journal_title:Anticancer research
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更新日期:2007-07-01 00:00:00
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journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2009-12-01 00:00:00
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journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2002-05-01 00:00:00
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journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2008-03-01 00:00:00
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journal_title:Anticancer research
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doi:
更新日期:2011-01-01 00:00:00
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journal_title:Anticancer research
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journal_title:Anticancer research
pub_type: 杂志文章
doi:
更新日期:2013-08-01 00:00:00
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journal_title:Anticancer research
pub_type: 杂志文章,评审
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更新日期:1987-07-01 00:00:00
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journal_title:Anticancer research
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journal_title:Anticancer research
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doi:
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journal_title:Anticancer research
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doi:
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journal_title:Anticancer research
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journal_title:Anticancer research
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更新日期:2005-11-01 00:00:00
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journal_title:Anticancer research
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更新日期:2009-02-01 00:00:00
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journal_title:Anticancer research
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更新日期:2003-05-01 00:00:00
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journal_title:Anticancer research
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journal_title:Anticancer research
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更新日期:2012-08-01 00:00:00
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journal_title:Anticancer research
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