Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

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

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

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

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.

    Book  Google Scholar 

  • 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.

    Google Scholar 

  • 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.

    Google Scholar 

  • 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.

Download references

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

Authors

Corresponding author

Correspondence to J M Angelastro.

Rights and permissions

Reprints 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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1209116

Keywords

This article is cited by

Search

Quick links