PMID- 19661320
OWN - NLM
STAT- MEDLINE
DCOM- 20090930
LR  - 20220330
IS  - 1791-7530 (Electronic)
IS  - 0250-7005 (Linking)
VI  - 29
IP  - 8
DP  - 2009 Aug
TI  - mTOR, S6 and AKT expression in relation to proliferation and apoptosis/autophagy 
      in glioma.
PG  - 3087-94
AB  - 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.
FAU - Annovazzi, Laura
AU  - Annovazzi L
AD  - Neuro-bio-oncology Center of Policlinico di Monza Foundation/University of Turin, 
      Vercelli, Italy.
FAU - Mellai, Marta
AU  - Mellai M
FAU - Caldera, Valentina
AU  - Caldera V
FAU - Valente, Guido
AU  - Valente G
FAU - Tessitore, Luciana
AU  - Tessitore L
FAU - Schiffer, Davide
AU  - Schiffer D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (BECN1 protein, human)
RN  - 0 (Beclin-1)
RN  - 0 (Ki-67 Antigen)
RN  - 0 (Membrane Proteins)
RN  - EC 2.3.2.27 (MIB1 ligase, human)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.4.2.30 (PARP1 protein, human)
RN  - EC 2.4.2.30 (Poly (ADP-Ribose) Polymerase-1)
RN  - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - *Apoptosis
MH  - Apoptosis Regulatory Proteins/metabolism
MH  - Autophagy
MH  - Beclin-1
MH  - Blotting, Western
MH  - Caspase 3/metabolism
MH  - *Cell Proliferation
MH  - Glioma/*metabolism/*pathology
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - Ki-67 Antigen/metabolism
MH  - Membrane Proteins/metabolism
MH  - Phosphorylation
MH  - Poly (ADP-Ribose) Polymerase-1
MH  - Poly(ADP-ribose) Polymerases/metabolism
MH  - Protein Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Ribosomal Protein S6 Kinases/*metabolism
MH  - TOR Serine-Threonine Kinases
MH  - Ubiquitin-Protein Ligases/metabolism
EDAT- 2009/08/08 09:00
MHDA- 2009/10/01 06:00
CRDT- 2009/08/08 09:00
PHST- 2009/08/08 09:00 [entrez]
PHST- 2009/08/08 09:00 [pubmed]
PHST- 2009/10/01 06:00 [medline]
AID - 29/8/3087 [pii]
PST - ppublish
SO  - Anticancer Res. 2009 Aug;29(8):3087-94.