Overexpression of c-MYC promotes an undifferentiated phenotype in cultured astrocytes and allows elevated Ras and Akt signaling to induce gliomas from GFAP-expressing cells in mice Journal Article


Authors: Lassman, A. B.; Dai, C.; Fuller, G. N.; Vickers, A. J.; Holland, E. C.
Article Title: Overexpression of c-MYC promotes an undifferentiated phenotype in cultured astrocytes and allows elevated Ras and Akt signaling to induce gliomas from GFAP-expressing cells in mice
Abstract: The c-MYC protooncogene is overexpressed in the most malignant primary brain tumor, glioblastoma multiforme (GBM), and has been correlated with the undifferentiated character of several cell types. However, the role of Myc activity in the generation of GBMs is not known. In this report, we show that gene transfer of c-MYC to GFAP-expressing astrocytes in vitro promotes the outgrowth of GFAP-negative, nestin-expressing cells with progenitor-like morphology, growth characteristics and gene-expression pattern. In addition, gene transfer of c-MYC to GFAP-expressing astrocytes in vivo induces GBMs when co-expressed with activated Ras and Akt. Without c-MYC, Ras+Akt induces GBMs from nestin-expressing CNS progenitors but is insufficient in GFAP-expressing differentiated astrocytes. The ability of Myc activity to enhance the oncogenic effects of Ras+Akt appears to be limited to GFAP-expressing astrocytes because nestin-expressing progenitors show no increase in GBM formation with the addition of MYC to Ras+Akt. These studies indicate that one role of MYC activity in the formation of gliomas might be to either promote or reinforce an undifferentiated phenotype required for glioma cells to respond to the oncogenic effects of elevated Ras and Akt activity.
Keywords: brain tumor; oncogene; mouse model; glioblastoma multiforme (gbm); rcas/tv-a
Journal Title: Neuron Glia Biology
Volume: 1
Issue: 2
ISSN: 1740-925X
Publisher: Cambridge University Press  
Date Published: 2004-05-01
Start Page: 157
End Page: 163
Language: English
ACCESSION: WOS:000207068600007
DOI: 10.1017/s1740925x04000249
PROVIDER: wos
PMCID: PMC1615889
PUBMED: 17047730
Notes: Article -- Source: Wos
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MSK Authors
  1. Andrew Lassman
    111 Lassman
  2. Eric Holland
    224 Holland
  3. Andrew J Vickers
    714 Vickers
  4. Chengkai Dai
    9 Dai