| Combined activation of Ras and Akt in neural progenitors induces glioblastoma formation in mice. | |
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MedLine Citation:
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PMID: 10802656 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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E C Holland; J Celestino; C Dai; L Schaefer; R E Sawaya; G N Fuller |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Nature genetics Volume: 25 ISSN: 1061-4036 ISO Abbreviation: Nat. Genet. Publication Date: 2000 May |
Date Detail:
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Created Date: 2000-06-12 Completed Date: 2000-06-12 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 9216904 Medline TA: Nat Genet Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 55-7 Citation Subset: IM |
Affiliation:
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Department of Neurosurgery, MD Anderson Cancer Center, Houston, Texas, USA. eholland@notes.mdacc.tmc.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Brain Neoplasms / enzymology, etiology, genetics* Cell Line, Transformed Enzyme Activation / genetics Gene Expression Regulation, Enzymologic* Gene Expression Regulation, Neoplastic* Glioblastoma / enzymology, etiology, genetics* Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Transgenic Protein-Serine-Threonine Kinases / genetics, metabolism Protein-Tyrosine Kinases / genetics, metabolism Proto-Oncogene Proteins / genetics*, metabolism* Proto-Oncogene Proteins c-akt ras Proteins / genetics*, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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CA16672/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Proto-Oncogene Proteins; EC 2.7.10.1/Protein-Tyrosine Kinases; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 3.6.5.2/ras Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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