Abstract:
:Glioblastoma multifome is the most common and most aggressive primary brain tumor with no current curative therapy. We found expression of the bZip transcription factor ATF5 in all 29 human glioblastomas and eight human and rat glioma cell lines assessed. ATF5 is not detectably expressed by mature brain neurons and astrocytes, but is expressed by reactive astrocytes. Interference with ATF5 function or expression in all glioma cell lines tested causes marked apoptotic cell death. In contrast, such manipulations do not affect survival of ATF5-expressing cultured astrocytes or of several other cell types that express this protein. In a proof-of-principle experiment, retroviral delivery of a function-blocking mutant form of ATF5 into a rat glioma model evokes death of the infected tumor cells, but not of infected brain cells outside the tumors. The widespread expression of ATF5 in glioblastomas and the selective effect of interference with ATF5 function/expression on their survival suggest that ATF5 may be an attractive target for therapeutic intervention in such tumors.
journal_name
Oncogenejournal_title
Oncogeneauthors
Angelastro JM,Canoll PD,Kuo J,Weicker M,Costa A,Bruce JN,Greene LAdoi
10.1038/sj.onc.1209116subject
Has Abstractpub_date
2006-02-09 00:00:00pages
907-16issue
6eissn
0950-9232issn
1476-5594pii
1209116journal_volume
25pub_type
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