PMID- 10802656
OWN - NLM
STAT- MEDLINE
DCOM- 20000612
LR  - 20240109
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 25
IP  - 1
DP  - 2000 May
TI  - Combined activation of Ras and Akt in neural progenitors induces glioblastoma 
      formation in mice.
PG  - 55-7
AB  - Gliomas are the most common primary malignant brain tumours and are classified 
      into four clinical grades, with the most aggressive tumours being grade 4 
      astrocytomas (also known as glioblastoma multiforme; GBM). Frequent genetic 
      alterations in GBMs (refs 2-5) result in stimulation of common signal 
      transduction pathways involving Ras, Akt and other proteins. It is not known 
      which of these pathways, if any, are sufficient to induce GBM formation. Here we 
      transfer, in a tissue-specific manner, genes encoding activated forms of Ras and 
      Akt to astrocytes and neural progenitors in mice. We found that although neither 
      activated Ras nor Akt alone is sufficient to induce GBM formation, the 
      combination of activated Ras and Akt induces high-grade gliomas with the 
      histological features of human GBMs. These tumours appear to arise after gene 
      transfer to neural progenitors, but not after transfer to differentiated 
      astrocytes. Increased activity of RAS is found in many human GBMs (ref. 11), and 
      we show here that Akt activity is increased in most of these tumours, implying 
      that combined activation of these two pathways accurately models the biology of 
      this disease.
FAU - Holland, E C
AU  - Holland EC
AD  - Department of Neurosurgery, MD Anderson Cancer Center, Houston, Texas, USA. 
      eholland@notes.mdacc.tmc.edu
FAU - Celestino, J
AU  - Celestino J
FAU - Dai, C
AU  - Dai C
FAU - Schaefer, L
AU  - Schaefer L
FAU - Sawaya, R E
AU  - Sawaya RE
FAU - Fuller, G N
AU  - Fuller GN
LA  - eng
GR  - CA16672/CA/NCI 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  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - Animals
MH  - Brain Neoplasms/enzymology/etiology/*genetics
MH  - Cell Line, Transformed
MH  - Enzyme Activation/genetics
MH  - *Gene Expression Regulation, Enzymologic
MH  - *Gene Expression Regulation, Neoplastic
MH  - Glioblastoma/enzymology/etiology/*genetics
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Protein Serine-Threonine Kinases/genetics/metabolism
MH  - Protein-Tyrosine Kinases/genetics/metabolism
MH  - Proto-Oncogene Proteins/*genetics/*metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - ras Proteins/*genetics/*metabolism
EDAT- 2000/05/10 09:00
MHDA- 2000/06/17 09:00
CRDT- 2000/05/10 09:00
PHST- 2000/05/10 09:00 [pubmed]
PHST- 2000/06/17 09:00 [medline]
PHST- 2000/05/10 09:00 [entrez]
AID - 10.1038/75596 [doi]
PST - ppublish
SO  - Nat Genet. 2000 May;25(1):55-7. doi: 10.1038/75596.