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.

  • Short Report
  • Published:

High level expression of ΔN-p63: a mechanism for the inactivation of p53 in undifferentiated nasopharyngeal carcinoma (NPC)?

Oncogene volume 19, pages 3439–3444 (2000)Cite this article

Abstract

Undifferentiated nasopharyngeal carcinoma (NPC) is an epithelial malignancy that is consistently associated with Epstein-Barr virus (EBV) but which very rarely has p53 gene mutations in primary tumours. Since the tumour suppressor p53 is mutated in most human cancers or the wild type protein is inactivated in a significant number of the remainder, here we have investigated cellular factors that could compromise p53 function in primary NPC. Twenty-five primary tumours were judged to carry only wild type p53 by SSCP analysis of all exons and sequence determination of exons 4–9. Only one tumour was found to express significant levels of hMdm2 and in 24/25 there were no detectable mutations or deletions in exons 1β and 2 of the p14ARF gene. However, immunohistochemistry consistently revealed that all the tumour cells express substantial amounts of the p53-related protein p63. Semi-quantitative RT–PCR analysis of mRNA from tumour biopsies showed that the dominant species expressed was invariably the truncated ΔN-isotype. Since this can block p53-mediated transactivation, it is potentially a dominant-negative isoform. In normal nasopharyngeal epithelium the distribution of p63 was restricted to the proliferating basal and suprabasal layers. We suggest that ΔN-p63 is a good candidate as a suppressor of wild type p53 function in these tumours and also that it may prove to be a valuable diagnostic marker for undifferentiated 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

Similar content being viewed by others

References

  • Alldred D, Clark G, Elledge R, Fuqua S, Brown R, Chamness G, Osborne G and McGuire W. . 1993 J. Natl. Cancer Inst. 85: 200–206.

  • Capoulade C, Bressac-de Paillerets B, Lefrere I, Ronsin M, Feuntun J, Tursz T and Wiels J. . 1998 Oncogene 16: 1603–1610.

  • Effert P, McCoy R, Abdel-Hamid M, Flynn K, Zhang Q, Bussion P, Tursz T, Liu E and Raab-Traub N. . 1992 J. Virol. 66: 3768–3775.

  • Eischen CM, Weber JD, Roussel MF, Sherr CJ and Cleveland JL. . 1999 Genes Dev. 13: 2658–2669.

  • Foulkes WD, Flanders TY, Pollock PM and Hayward NK. . 1997 Mol. Med. 3: 5–20.

  • Fries KL, Miller WE and Raab-Traub N. . 1996 J. Virol. 70: 8653–8659.

  • Gazzeri S, Gouyer V, Vourch C, Brambilla C and Brambilla E. . 1998 Oncogene 16: 497–504.

  • Gulley ML, Nicholls JM, Schneider BG, Amin MB, Ro JY and Geradts J. . 1998 Am. J. Pathol. 152: 865–869.

  • Haupt Y, Maya R, Kazaz A and Oren M. . 1997 Nature 387: 296–299.

  • Klein G. . 1979 The Epstein-Barr virus. Epstein MA and Achong BG (eds). Springer-Verlag: Berlin.

  • Kaelin Jr WG. . 1999 Oncogene 18: 7701–7705.

  • Kaghad M, Bonnet H, Yang A, Creancier L, Biscan J-C, Valent A, Minty A, Chalon P, Lelias J-M, Dumont X, Ferrara P, McKeon F and Caput D. . 1997 Cell 90: 809–819.

  • Kubbutat MHG, Jones SN and Vousden KH. . 1997 Nature 387: 299–303.

  • Levine A. . 1997 Cell 88: 323–331.

  • Lo KW, Cheung ST, Leung SF, van Hasselt A, Mak KF, Chung YF, Woo JK, Lee JC and Huang DP. . 1996 Cancer Res. 56: 2721–2725.

  • Lo KW, Huang DP and Lau KM. . 1995 Cancer Res. 55: 2039–2043.

  • Lo KW, Mok CH, Huang DP, Liu YX, Choi PH, Lee JC and Tsao SW. . 1992 Anticancer Res. 12: 1957–1963.

  • McGregor JM, Berkhout RJ, Rozycka M, Schegget J, Bouwes Bavinck JN, Brooks L and Crook T. . 1997 Oncogene 15: 1737–1740.

  • Mills AA, Zheng B, Wang X-J, Vogel H, Roop D and Bradley A. . 1999 Nature 398: 708–713.

  • Murono S, Yoshizaki T, Park CS and Furukawa M. . 1999 Histopathology 34: 432–438.

  • Niedobitek G, Agathanggelou A, Barber P, Smallman LA, Jones EL and Young LS. . 1993 J. Pathol. 170: 457–461.

  • Niedobitek G, Agathanggelou A and Nicholls JM. . 1996 Semin. Cancer Biol. 7: 165–174.

  • Oliner JD, Kinzler KW, Meltzer PS, George D and Vogelstein B. . 1992 Nature 358: 80–83.

  • Oliner JD, Pietenpol JA, Thiagalingam S, Gyuris J, Kinzler KW and Vogelstein . 1993 Nature 362: 857–860.

  • Parsa R, Yang A, McKeon F and Green H. . 1999 J. Invest. Dermatol. 113,

  • Quelle DE, Zindy F, Ashmun R and Sherr CJ. . 1995 Cell 83: 993–1000.

  • Quelle DE, Cheng M, Ashmun RA and Sherr CJ. . 1997 Proc. Natl. Acad. Sci. USA 94: 3436–3440.

  • Rickinson A and Kieff E. . 1996 Fields Virology, 3rd edition. Fields BN, Knipe DM, Howley PM et al. (eds).. Lippincott-Raven Publishers: Philadelphia.

  • Ruas M and Peters G. . 1998 Biochim. Biophys. Acta. 1378: F115–F177.

  • Sherr CJ. . 1998 Genes Dev. 12: 2984–2991.

  • Schmitt CA, McCurrach ME, de Stachina E, Wallace-Brodeur RR and Lowe SW. . 1999 Genes Dev. 13: 2670–2677.

  • Sheu LF, Chen A, Tseng HH, Leu FJ, Lin JK, Ho KC and Meng CL. . 1995 Human Pathol. 26: 380–386.

  • Spruck CH, Tsai TC, Huang DP, Yang AS, Rideout WM, Gonzalez-Zulueta M, Choi P, Lo KW, Yu MC and Jones PA. . 1992 Cancer Res. 52: 4787–4790.

  • Stott FJ, Bates S, James MC, McConnell BB, Starborg M, Brookes S, Palmero I, Ryan K, Hara E, Vousden KH and Peters G. . 1998 EMBO J. 17: 5001–5014.

  • Sun Y, Hegamyer G, Cheng YJ, Hildesheim A, Chen J-Y, Chen I-H, Cao Y, Kai-Tai Y and Colburn NH. . 1992 Proc. Natl. Acad. Sci. USA 89: 6516–6520.

  • Sun Y, Hilesheim A, Lanier AE, Cao Y, Yao KT, Raab-Traub N and Yang CS. . 1995 Oncogene 10: 785–788.

  • Vousden KH. . 1993 FASEB J. 7: 872–879.

  • Yang A, Kaghad M, Wang Y, Gillet E, Flemming MD, Dotsch V, Andrews NC, Caput D and McKeon F. . 1998 Mol. Cell. 2: 305–316.

  • Yang A, Schweitzer R, Sun D, Kaghad M, Walker N, Bronson RT, Tabin C, Sharpe A, Caput D, Crum C and McKeon F. . 1999 Nature 398: 714–718.

  • Zhang Y and Xiong Y. . 1999 Mol. Cell. 3: 579–591.

  • Zhang Y, Xiong Y and Yarborough WG. . 1998 Cell 92: 725–734.

  • Zindy F, Eischen CM, Randle DH, Kamijo T, Cleveland JL, Sherr CJ and Roussel MF. . 1998 Genes Dev. 12: 2424–2433.

Download references

Acknowledgements

We would like to thank Barry Gusterson (Institute of Cancer Research, London) for his advice and help in the production of digital images in Figures 2 and 3.

Author information

Author notes

  1. Tim Crook and John M Nicholls: T Crook and JM Nicholls contributed equally to this study

Authors and Affiliations

  1. Ludwig Institute for Cancer Research and Section of Virology and Cell Biology, Imperial College of Science, Technology and Medicine, St Mary's Campus, Norfolk Place, London, W2 1PG, UK

    Tim Crook, Jenny O'Nions & Martin J Allday

  2. Department of Pathology, University of Hong Kong, Queen Mary Hospital, Hong Kong, People's Republic of China

    John M Nicholls

  3. Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1 7HT, UK

    Louise Brooks

Authors
  1. Tim Crook
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. John M Nicholls
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Louise Brooks
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jenny O'Nions
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Martin J Allday
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Crook, T., Nicholls, J., Brooks, L. et al. High level expression of ΔN-p63: a mechanism for the inactivation of p53 in undifferentiated nasopharyngeal carcinoma (NPC)?. Oncogene 19, 3439–3444 (2000). https://doi.org/10.1038/sj.onc.1203656

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1203656

Keywords

This article is cited by

Search

Advanced search

Quick links