Selective destruction of glioblastoma cells by interference with the activity or expression of ATF5

James M Angelastro, P. D. Canoll, J. Kuo, M. Weicker, A. Costa, J. N. Bruce, L. A. Greene

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)907-916
Number of pages10
JournalOncogene
Volume25
Issue number6
DOIs
StatePublished - Feb 9 2006

Fingerprint

Glioblastoma
Glioma
Astrocytes
Cell Line
Neoplasms
Survival
Brain
Brain Neoplasms
Cell Death
Transcription Factors
Neurons
Therapeutics
Proteins

Keywords

  • Apoptosis
  • Astrocytes
  • ATF5
  • Brain tumor
  • Glioma

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Angelastro, J. M., Canoll, P. D., Kuo, J., Weicker, M., Costa, A., Bruce, J. N., & Greene, L. A. (2006). Selective destruction of glioblastoma cells by interference with the activity or expression of ATF5. Oncogene, 25(6), 907-916. https://doi.org/10.1038/sj.onc.1209116

Selective destruction of glioblastoma cells by interference with the activity or expression of ATF5. / Angelastro, James M; Canoll, P. D.; Kuo, J.; Weicker, M.; Costa, A.; Bruce, J. N.; Greene, L. A.

In: Oncogene, Vol. 25, No. 6, 09.02.2006, p. 907-916.

Research output: Contribution to journalArticle

Angelastro, JM, Canoll, PD, Kuo, J, Weicker, M, Costa, A, Bruce, JN & Greene, LA 2006, 'Selective destruction of glioblastoma cells by interference with the activity or expression of ATF5', Oncogene, vol. 25, no. 6, pp. 907-916. https://doi.org/10.1038/sj.onc.1209116
Angelastro, James M ; Canoll, P. D. ; Kuo, J. ; Weicker, M. ; Costa, A. ; Bruce, J. N. ; Greene, L. A. / Selective destruction of glioblastoma cells by interference with the activity or expression of ATF5. In: Oncogene. 2006 ; Vol. 25, No. 6. pp. 907-916.
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