Carcinogenesis, Vol 19, 1529-1537, Copyright © 1998 by Oxford University Press
SC Barnett, L Robertson, D Graham, D Allan and R Rampling
The oligodendrocyte-type-2 astrocyte lineage (O-2A) comprises a progenitor
cell that is able to differentiate into an oligodendrocyte or astrocyte in
vitro. The lineage was originally identified in the neonatal rat central
nervous system but evidence suggests that the equivalent O-2A lineage also
exists in humans. Apart from its putative and widely studied role in glial
repair, this cell type could potentially be involved in malignant glioma
formation. In this study we demonstrate that a rat O-2A progenitor cell
line carrying the bacterial beta-galactosidase reporter gene and
transformed with the c-myc and H- ras oncogenes which has lost its
differentiation capacity in vitro generates glioma-like growth after
stereotactic injection into the adult rat brain. Tumour pathology was
similar to human glioblastoma, suggesting that one of the pathways in the
generation of human glioblastomas may be the transformation of adult O-2A
progenitor cells. Parallel studies demonstrated the presence of a
DNA-binding protein complex, termed APprog, in a panel of human glioma cell
lines. This protein was initially identified in O-2A progenitor cells and
not their differentiated progeny. These data lead us to propose that APprog
could be used as an indicator of the lineage origin of gliomas.
ARTICLES
Oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells transformed with c-myc and H-ras form high-grade glioma after stereotactic injection into the rat brain
Department of Neurology, University of Glasgow, UK. gpma37@udcf.gla.ac.uk
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