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Combined activation of Ras and Akt in neural progenitors induces glioblastoma formation in mice
Ist Teil von
Nature genetics, 2000-05, Vol.25 (1), p.55-57
Ort / Verlag
London: Nature Publishing Group
Erscheinungsjahr
2000
Quelle
MEDLINE
Beschreibungen/Notizen
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.