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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Aiello L, Guilfoyle R, Huebner K, Weinmann R . (1979). Virology 94: 460–469.
Angelastro JM, Ignatova TN, Kukekov VG, Steindler DA, Stengren GB, Mendelsohn C et al. (2003). J Neurosci 23: 4590–4600.
Angelastro JM, Mason JL, Ignatova TN, Kukekov VG, Stengren GB, Goldman JE et al. (2005). J Neurosci 25: 3889–3899.
Angelastro JM, Moon NY, Liu DX, Yang AS, Greene LA, Franke TF . (2001). J Biol Chem 276: 12190–12200.
Asai A, Miyagi Y, Sugiyama A, Gamanuma M, Hong SH, Takamoto S et al. (1994). J Neurooncol 19: 259–268.
Badie B, Goh CS, Klaver J, Herweijer H, Boothman DA . (1999). Cancer Gene Ther 6: 155–162.
Benda P, Lightbody J, Sato G, Levine L, Sweet W . (1968). Science 161: 370–371.
Canman CE . (2001). Curr Biol 11: R121–R124.
Castedo M, Perfettini JL, Roumier T, Andreau K, Medema R, Kroemer G . (2004). Oncogene 23: 2825–2837.
Collins VP . (2004). J Neurol Neurosurg Psychiatry 75(Suppl 2): ii2–ii11.
Dai C, Holland EC . (2001). Biochim Biophys Acta 1551: M19–M27.
Deshmukh M, Vasilakos J, Deckwerth TL, Lampe PA, Shivers BD, Johnson Jr EM . (1996). J Cell Biol 135: 1341–1354.
Hansen MB, Mitchelmore C, Kjaerulff KM, Rasmussen TE, Pedersen KM, Jensen NA . (2002). Genomics 80: 344–350.
Hirose Y, Berger MS, Pieper RO . (2001). Cancer Res 61: 5843–5849.
Jensen AM, Chiu SY . (1991). J Neurosci 11: 1674–1684.
Kleihues P, Burger P, Sheithauer B . (1993). Histology Typing of Tumours of the Central Nervous System. Berlin: Springer-Verlag.
Ko L, Koestner A, Wechsler W . (1980). Acta Neuropathol (Berl) 51: 23–31.
Kruse CA, Mitchell DH, Kleinschmidt-DeMasters BK, Franklin WA, Morse HG, Spector EB et al. (1992). In Vitro Cell Dev Biol 28A: 609–614.
Levison SW, McCarthy DK . (1991). Astroglia in Culture. Cambridge: MIT Press, pp 309–336.
Maher EA, Furnari FB, Bachoo RM, Rowitch DH, Louis DN, Cavenee WK et al. (2001). Genes Dev 15: 1311–1333.
Mason JL, Angelastro JM, Ignatova TN, Kukekov VG, Lin G, Greene LA et al. (2005). Mol Cell Neurosci 29: 372–380.
McLendon R, Enterline D, Tien R, Thorstad W, Bruner J . (1998). In: Bigner D, McLendon R, Bruner J (eds). Russell and Rubinstein's Pathology of Tumors of the Nervous System, Chapter 9, Oxford University Press: New York, pp 307–571.
Nishizawa M, Nagata S . (1992). FEBS Lett 299: 36–38.
Pati D, Meistrich ML, Plon SE . (1999). Mol Cell Biol 19: 5001–5013.
Persengiev SP, Devireddy LR, Green MR . (2002). Genes Dev 16: 1806–1814.
Pinkerton H, Rana MW . (1976). Proc Soc Exp Biol Med 151: 532–534.
Ponten J, Macintyre EH . (1968). Acta Pathol Microbiol Scand 74: 465–486.
Qi Y, Wang JK, McMillian M, Chikaraishi DM . (1997). J Neurosci 17: 1217–1225.
Rasheed BK, Wiltshire RN, Bigner SH, Bigner DD . (1999). Curr Opin Oncol 11: 162–167.
Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T et al. (2004). Nature 432: 396–401.
Sonoda Y, Ozawa T, Hirose Y, Aldape KD, McMahon M, Berger MS et al. (2001). Cancer Res 61: 4956–4960.
Vogelbaum MA, Tong JX, Perugu R, Gutmann DH, Rich KM . (1999). J Neurosurg 91: 483–489.
Yamagishi N, Miyakoshi J, Ohtsu S, Day III RS, Takebe H . (1995). J Radiat Res (Tokyo) 36: 239–247.
Acknowledgements
This work was supported in part by grants from the NIH-NINDS (LAG and PDC), American Brain Tumor Association (JNB and MW), and American Cancer Society Institutional Award (JMA). We thank Rachel Ventura and Grace Lin for assistance in culturing astrocytes, Angelo Arias for the BrdU incorporation experiments, and Claudine Bitel and Yi-Ji Shi for their superb technical assistance, as well as Dr James E Goldman for helpful discussions.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Angelastro, J., Canoll, P., Kuo, J. et al. Selective destruction of glioblastoma cells by interference with the activity or expression of ATF5. Oncogene 25, 907–916 (2006). https://doi.org/10.1038/sj.onc.1209116
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1209116
Keywords
This article is cited by
-
Activating transcription factor 5 (ATF5) promotes tumorigenic capability and activates the Wnt/b-catenin pathway in bladder cancer
Cancer Cell International (2021)
-
Influence of genetic variants in asparaginase pathway on the susceptibility to asparaginase-related toxicity and patients' outcome in childhood acute lymphoblastic leukemia
Cancer Chemotherapy and Pharmacology (2021)
-
Critical role of HOX transcript antisense intergenic RNA (HOTAIR) in gliomas
Journal of Molecular Medicine (2020)
-
Dominant-negative ATF5 rapidly depletes survivin in tumor cells
Cell Death & Disease (2019)
-
The neuroprotective transcription factor ATF5 is decreased and sequestered into polyglutamine inclusions in Huntington’s disease
Acta Neuropathologica (2017)