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:

Epstein–Barr virus-encoded small RNA induces insulin-like growth factor 1 and supports growth of nasopharyngeal carcinoma-derived cell lines

Oncogene volume 24, pages 1767–1773 (2005)Cite this article

Abstract

To assess the role of insulin-like growth factor 1 (IGF-1) in the growth of nasopharyngeal carcinoma (NPC), three NPC-derived cell lines, C666-1, CNE1 and HONE1, were examined. C666-1 cells maintained NPC phenotype of Epstein–Barr virus (EBV) expression and were positive for IGF-1 secretion, and their growth was strikingly inhibited by treatment with an anti-IGF-1 antibody under low serum condition. On the other hand, CNE1 and HONE1 cells were EBV-negative and did not secrete IGF-1. Although they could not grow under low serum condition, addition of recombinant IGF-1 made them grow. EBV conversion of CNE1 and HONE1 cells reproduced NPC phenotype of EBV expression and accompanied IGF-1 expression. Although they could grow under low serum condition, their growth was strikingly inhibited by treatment with the anti-IGF-1 antibody. These results suggest that EBV infection induces IGF-1 in NPC cell lines, and that the secreted IGF-1 acts as an autocrine growth factor. These findings seem to be operative in vivo, as NPC biopsies consistently express IGF-1. Further studies demonstrated that increased IGF-1 expression reflected transcriptional activation, and EBV-encoded small RNA (EBER) was responsible for IGF-1 induction. EBER is invariably expressed in EBV-associated malignancies, including NPC. The present findings strongly suggest that EBER directly affects the pathogenesis of NPC.

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

Access options

Buy this article

  • Purchase on Springer Link
  • 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
Figure 6

Similar content being viewed by others

References

  • Cheung ST, Huang DP, Hui AB, Lo KW, Ko CW, Tsang YS, Wong N, Whitney BM and Lee JC . (1999). Int. J. Cancer, 83, 121–126.

  • Fürstenberger G and Senn H-J . (2002). Lancet Oncol., 3, 298–302.

  • Imai S, Nishikawa J and Takada K . (1998). J. Virol., 72, 4371–4378.

  • Iwakiri D, Eizuru Y, Tokunaga M and Takada K . (2003). Cancer Res., 63, 7062–7067.

  • Kieff E and Rickinson AB . (2002). Fields Virology 4th edn. Fields BN, Knipe DM and Howley PM (eds). Lippincott-Raven Publishers: Philadelphia, pp. 2511–2573.

    Google Scholar 

  • Kitagawa N, Goto M, Kurozumi K, Maruo S, Fukayama M, Naoe T, Yasukawa M, Hino K, Suzuki T, Todo M and Takada K . (2000). EMBO J., 19, 6742–6750.

  • Komano J, Maruo S, Kurozumi K and Takada K . (1999). J. Virol., 73, 9827–9831.

  • Maruo S, Yang L and Takada K . (2001). J. Gen. Virol., 82, 2373–2383.

  • Nanbo A, Inoue K, Adachi-Takasawa K and Takada K . (2002). EMBO J., 5, 954–965.

  • Rickinson AB and Kieff E . (2002). Fields Virology 4th edn. Fields BN, Knipe DM and Howley PM (eds). Lippincott-Raven Publishers: Philadelphia, pp. 2575–2627.

    Google Scholar 

  • Sharp TV, Schwemmle M, Jeffrey I, Laing K, Mello H, Proud CG, Hilse K and Clemens MJ . (1993). Nucleic Acids Res., 21, 4483–4490.

  • Yamamoto N, Takizawa T, Iwanaga Y, Shimizu N and Yamamoto N . (2000). FEBS Lett., 484, 153–158.

  • Yao K, Zhang H-Y, Zhu H-C, Wang F-X, Li G-Y, Wen D-S, Li Y-P, Tsa C-HA and Glaser R . (1990). Cancer, 45, 83–89.

  • Yu H and Rohan T . (2000). J. Natl. Cancer Inst., 92, 1472–1489.

  • Zeng S, Wu Y, Zeng Y, Zech L and Klein G . (1982). Hereditas, 97, 23–28.

Download references

Acknowledgements

We thank B Sugden and T Sculley for helpful discussions and critical reading of the manuscript. We also thank Y Ando for technical assistance. This work was supported by grants-in-aid from the Ministry of Education, Science, Sports, Culture, and Technology, Japan, and from the Uehara Memorial Foundation.

Author information

Authors and Affiliations

  1. Department of Tumor Virology, Institute for Genetic Medicine, Hokkaido University, N15 W7, Kita-ku, Sapporo, 060-0815, Japan

    Dai Iwakiri & Kenzo Takada

  2. Department of Otolaryngology, College of Medicine, National Taiwan University, Taipei, Taiwan

    Tzung-Shiahn Sheen

  3. Department of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan

    Jen-Yan Chen

  4. Department of Clinical Oncology, Chinese University of Hong Kong, Hong Kong, China

    Dolly Poon Huang

Authors
  1. Dai Iwakiri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tzung-Shiahn Sheen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jen-Yan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dolly Poon Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kenzo Takada
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kenzo Takada.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Iwakiri, D., Sheen, TS., Chen, JY. et al. Epstein–Barr virus-encoded small RNA induces insulin-like growth factor 1 and supports growth of nasopharyngeal carcinoma-derived cell lines. Oncogene 24, 1767–1773 (2005). https://doi.org/10.1038/sj.onc.1208357

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1208357

Keywords

This article is cited by

Search

Advanced search

Quick links