PMID- 9799739
OWN - NLM
STAT- MEDLINE
DCOM- 19981209
LR  - 20240109
IS  - 0960-9822 (Print)
IS  - 0960-9822 (Linking)
VI  - 8
IP  - 21
DP  - 1998 Oct 22
TI  - Protein kinase B (PKB/Akt) activity is elevated in glioblastoma cells due to 
      mutation of the tumor suppressor PTEN/MMAC.
PG  - 1195-8
AB  - Glioblastomas are highly malignant tumors of the central nervous system that are 
      resistant to radiation and chemotherapy [1]. We explored the role of the 
      phosphatidylinositol (PI) 3-kinase signal transduction pathway in glioblastomas, 
      as this pathway has been shown to inhibit apoptosis induced by cytokine 
      withdrawal and the detachment of cells from the extracellular matrix [2]. 
      Components of this pathway have been implicated in tumor development [3-6]. We 
      show that glioblastoma cells, in contrast to primary human astrocytes, contain 
      high endogenous protein kinase B (PKB/Akt) activity and high levels of PI 
      3,4,5-triphosphate (PI(3,4,5)P3) and PI(3,4)P2, the lipid products of PI 
      3-kinase. These glioblastoma cells express mutant forms of the putative 3' 
      phospholipid phosphatase PTEN, also known as MMAC. Expression of wild-type PTEN 
      derived from primary astrocytes, but not of mutant forms of PTEN, reduced the 
      levels of 3' phosphoinositides and inhibited PKB/Akt activity. PTEN antagonized 
      the activation of PKB/Akt by growth factors, by activated PI 3-kinase and by 
      PI-dependent protein kinase-1 (PDK1), but did not antagonize the 
      phospholipid-independent activation of PKB/Akt lacking the pleckstrin homology 
      (PH) domain. These results suggest a role for PTEN in regulating the activity of 
      the PI 3-kinase pathway in malignant human cells.
FAU - Haas-Kogan, D
AU  - Haas-Kogan D
AD  - Department of Radiation Oncology University of California San Francisco, 
      California, 94115, USA. hkogan@radonc17.ucsf.edu
FAU - Shalev, N
AU  - Shalev N
FAU - Wong, M
AU  - Wong M
FAU - Mills, G
AU  - Mills G
FAU - Yount, G
AU  - Yount G
FAU - Stokoe, D
AU  - Stokoe D
LA  - eng
GR  - MO1RR01271/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Curr Biol
JT  - Current biology : CB
JID - 9107782
RN  - 0 (Phosphatidylinositol Phosphates)
RN  - 0 (Phospholipids)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.11.1 (3-Phosphoinositide-Dependent Protein Kinases)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (PDPK1 protein, human)
RN  - EC 2.7.11.1 (Pdpk1 protein, mouse)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.1.3.2 (Phosphoric Monoester Hydrolases)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (PTEN protein, human)
SB  - IM
MH  - 3-Phosphoinositide-Dependent Protein Kinases
MH  - 3T3 Cells
MH  - Animals
MH  - Astrocytes/metabolism
MH  - COS Cells
MH  - Enzyme Activation
MH  - *Genes, Tumor Suppressor
MH  - Glioblastoma/*enzymology/*genetics
MH  - Humans
MH  - Mice
MH  - *Mutation
MH  - PTEN Phosphohydrolase
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphatidylinositol Phosphates/metabolism
MH  - Phospholipids/metabolism
MH  - Phosphoric Monoester Hydrolases/*genetics
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Protein-Tyrosine Kinases/genetics/metabolism
MH  - Proto-Oncogene Proteins/*genetics/*metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Recombinant Proteins/metabolism
MH  - Transfection
MH  - *Tumor Suppressor Proteins
EDAT- 1998/11/04 00:00
MHDA- 1998/11/04 00:01
CRDT- 1998/11/04 00:00
PHST- 1998/11/04 00:00 [pubmed]
PHST- 1998/11/04 00:01 [medline]
PHST- 1998/11/04 00:00 [entrez]
AID - S0960-9822(07)00493-9 [pii]
AID - 10.1016/s0960-9822(07)00493-9 [doi]
PST - ppublish
SO  - Curr Biol. 1998 Oct 22;8(21):1195-8. doi: 10.1016/s0960-9822(07)00493-9.