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 Paper
  • Published:

High activin A-expression in human neuroblastoma: suppression of malignant potential and correlation with favourable clinical outcome

Oncogene volume 24, pages 680–687 (2005)Cite this article

Abstract

Amplification of the MYCN oncogene contributes to the malignant progression of human neuroblastomas, but the mechanisms have remained unclear. We have previously demonstrated that N-Myc facilitates angiogenesis by downregulating an angiogenesis inhibitor identified as the inhibin βA homodimer activin A. Here, we have sought to define the molecular, biological and clinical consequences of activin A expression in human neuroblastoma. We report that enhanced activin A expression suppresses proliferation and colony formation of human neuroblastoma cells with amplified MYCN in vitro; that it inhibits neuroblastoma growth and angiogenesis in vivo; that it is highly expressed in differentiated, but not undifferentiated human neuroblastomas; and that it correlates with favourable outcome of neuroblastoma patients. Our results indicate that high activin A expression plays an important beneficial role in human neuroblastoma.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

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

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

Abbreviations

du:

density units

EFS:

cumulative event-free survival rate after 5 years

GAPDH:

glyceraldehyde-3-phosphate dehydrogenase

IGF:

insulin-like growth factor

INHBA:

inhibin βA

NB:

neuroblastoma

TGF:

transforming growth factor

TrkA/B:

tyrosine receptor kinase A or B, respectively

VIP:

vasoactive intestinal peptide

References

  • Altaba ARI and Melton DA . (1989). Nature, 341, 33–38.

  • Andreasson K and Worley PF . (1995). Neuroscience, 69, 781–796.

  • Breit S, Ashman K, Wilting J, Rössler J, Hatzi E, Fotsis T and Schweigerer L . (2000). Cancer Res., 60, 4596–4601.

  • Brodeur GM . (2003). Nat. Rev. Cancer, 3, 203–216.

  • Brodeur GM, Pritchard J, Berthold F, Carlsen NLT, Castel V, Castleberry RP, De Bernardi B, Evans AE, Favrot M, Hedborg F, Kaneko M, Kemshead J, Lampert F, Lee REJ, Look AT, Pearson ADJ, Philip T, Roald B, Sawada T, Seeger RC, Tsuchida Y and Voute PA . (1993). J. Clin. Oncol., 11, 1466–1477.

  • Cantero R, Torres AJ, Maestro M, Fernandez C, Hernando F, del Barco V, Sanz T and Balibrea JL . (1999). World J. Surg., 23, 1294–1299; discussion 1299–1300.

  • Chen YG, Lui HM, Lin SL, Lee JM and Ying SY . (2002). Exp. Biol. Med. (Maywood), 227, 75–87.

  • Chomczynski P . (1993). Biotechniques, 15, 532–534, 536–537.

  • Cinatl Jr J, Kotchetkov R, Blaheta R, Driever PH, Vogel JU and Cinatl J . (2002). Int. J. Oncol., 20, 97–106.

  • Fotsis T, Breit S, Lutz W, Rössler J, Hatzi E, Schwab M and Schweigerer L . (1999). Eur. J. Biochem., 263, 757–764.

  • Fotsis T, Pepper MS, Aktas E, Breit S, Rasku S, Adlercreutz H, Wähälä K, Montesano R and Schweigerer L . (1997). Cancer Res., 57, 2916–2921.

  • Giusti AF, Hinman VF, Degnan SM, Degnan BM and Morse DE . (2000). Evol. Dev., 2, 294–302.

  • Hermanson O, Sugihara TM and Andersen B . (1999). Cell. Mol. Biol. (Noisy-le-grand), 45, 677–686.

  • Hübner G and Werner S . (1996). Exp. Cell. Res., 228, 106–113.

  • Iwahori Y, Saito H, Torii K and Nishiyama N . (1997). Brain Res., 760, 52–58.

  • Mather JP, Moore A and Li R-H . (1997). Proc. Soc. Exp. Biol. Med., 215, 209–222.

  • Rössler J, Breit S, Havers W and Schweigerer L . (1999). Int. J. Cancer, 81, 113–117.

  • Schweigerer L, Breit S, Wenzel A, Tsunamoto K, Ludwig R and Schwab M . (1990). Cancer Res., 50, 4411–4416.

  • Schweigerer L, Neufeld G, Friedman J, Abraham JA, Fiddes JC and Gospodarowicz D . (1987). Nature, 325, 257–259.

  • Tuuri T, Erämaa M, Van Schaik RHN and Ritvos O . (1996). Mol. Cell. Endocrinol., 121, 1–10.

  • Visvader JE, Venter D, Hahm K, Santamaria M, Sum EY, O'Reilly L, White D, Williams R, Armes J and Lindeman GJ . (2001). Proc. Natl. Acad. Sci. USA, 98, 14452–14457.

  • Wai DH, Schaefer KL, Schramm A, Korsching E, Van Valen F, Ozaki T, Boecker W, Schweigerer L, Dockhorn-Dworniczak B and Poremba C . (2002). Int. J. Oncol., 20, 441–451.

  • Westermann F and Schwab M . (2002). Cancer Lett., 184, 127–147.

  • Woodruff TK, Sluss P, Wang E, Janssen I and Mersol-Barg MS . (1997). J. Endocrinol., 152, 167–174.

  • Wu DD, Lai M, Hughes PE, Sirimanne E, Gluckman PD and Williams CE . (1999). Brain Res., 835, 369–378.

Download references

Acknowledgements

This work was supported by a grant from the Wilhelm-Sander-Stiftung to LS. We thank Professor Theodore Fotsis for sharing unpublished data, Ruth Frenk and Stefanie Paschen for excellent technical assistance and Drs Stephen Breit, Ludger Klein-Hitpaß, and Daniel Wai for help with transfection studies or sharing their knowledge on microarray analysis.

Author information

Author notes

  1. Alexander Schramm and Volker von Schuetz: These authors contributed equally to this work

Authors and Affiliations

  1. Abt. Hämatologie, Onkologie und Endokrinologie, Universitäts-Kinderklinik Essen, Germany

    Alexander Schramm, Volker von Schuetz & Werner Havers

  2. Universitäts-Kinderklinik Marburg, Germany

    Holger Christiansen

  3. Abt. Pädiatrie I, Zentrum für Kinderheilkunde und Jugendmedizin, Klinikum der Georg-August-Universität Göttingen, Germany

    Maria Papoutsi, Jörg Wilting & Lothar Schweigerer

Authors
  1. Alexander Schramm
    View author publications

    Search author on:PubMed Google Scholar

  2. Volker von Schuetz
    View author publications

    Search author on:PubMed Google Scholar

  3. Holger Christiansen
    View author publications

    Search author on:PubMed Google Scholar

  4. Werner Havers
    View author publications

    Search author on:PubMed Google Scholar

  5. Maria Papoutsi
    View author publications

    Search author on:PubMed Google Scholar

  6. Jörg Wilting
    View author publications

    Search author on:PubMed Google Scholar

  7. Lothar Schweigerer
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Lothar Schweigerer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schramm, A., Schuetz, V., Christiansen, H. et al. High activin A-expression in human neuroblastoma: suppression of malignant potential and correlation with favourable clinical outcome. Oncogene 24, 680–687 (2005). https://doi.org/10.1038/sj.onc.1208087

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/sj.onc.1208087

Keywords

This article is cited by

Search

Advanced search

Quick links