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:

Senescing oral dysplasias are not immortalized by ectopic expression of hTERT alone without other molecular changes, such as loss of INK4A and/or retinoic acid receptor-β: but p53 mutations are not necessarily required

Oncogene volume 22, pages 7804–7808 (2003)Cite this article

Abstract

Our previous work showed that acquisition of immortality at the dysplasia stage of oral cancer progression was consistently associated with four changes: loss of retinoic acid receptor (RAR)-β and p16INK4A expression, p53 mutations and activation of telomerase. One atypical dysplasia (D17) that underwent delayed senescence after an extended lifespan showed loss of RAR-β and p16INK4A/p14ARF expression, but retained functional wild-type p53 and telomerase was not activated. We now demonstrate that retroviral delivery of hTERT results in telomere lengthening and immortalization of D17 without loss of functional wild-type p53 activity. In contrast, the expression of hTERT in two other typical mortal dyplasia cultures (that retain RAR-β and p16INK4A expression) does not extend their lifespan, even though telomeres are lengthened.

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

  • Campisi J . (2000). In vivo, 14, 183–188.

  • Ghose A, Fleming J, El-Bayoumy K and Harrison PR . (2001). Cancer Res., 61, 7479–7487.

  • Gordon KE, Ireland H, Roberts M, Steegs K, McCaul JA, MacDonald DG and Parkinson KE . (2002). Cancer Res., 63, 458–467.

  • Kresty LA, Mallery SR, Knobloch TJ, Song H, Lloyd M, Casto BC and Weghorst CM . (2002). Cancer Res., 62, 5295–5300.

  • Lustig AJ . (1999). Proc. Natl. Acad. Sci. USA, 96, 3339–3341.

  • McGregor F, Muntoni A, Fleming J, Brown J, Felix DH, MacDonald G, Parkinson EK and Harrison PR . (2002). Cancer Res., 62, 4757–4766.

  • McGregor F, Wagner E, Felix D, Soutar D, Parkinson K and Harrison PR . (1997). Cancer Res., 57, 3886–3889.

  • Morris M, Hepburn P and Wynford-Thomas D . (2002). Oncogene, 21, 4277–4288.

  • Munro J, Steeghs K, Morrison V, Ireland H and Parkinson EK . (2001). Oncogene, 20, 3541–3552.

  • Munro J, Stott FJ, Vousden KH, Peters G and Parkinson EK . (1999). Cancer Res., 59, 2516–2521.

  • Ohtani N, Zebedee Z, Huot TJ, Stinson JA, Sugimoto M, Ohashi Y, Sharrocks AD, Peters G and Hara E . (2001). Nature, 409, 1067–1070.

  • Pandita TK . (2002). Oncogene, 21, 611–618.

  • Papadimitrakopoulou V, Izzo J, Lippman SM, Lee JS, Fan YH, Clayman G, Ro JY, Hittelman WN, Lotan R, Hong WK and Mao L . (1997). Oncogene, 14, 1799–1803.

  • Ramirez RD, Morales CP, Herbert BS, Rohde JM, Passons C, Shay JW and Wright WE . (2001). Genes Dev., 15, 398–403.

  • Rheinwald JG and Beckett MA . (1981). Cancer Res., 41, 1657–1663.

  • Rheinwald JG, Hahn WC, Ramsey MR, Wu JY, Guo Z, Tsao H, De Luca M, Catricala C and O'Toole KM . (2002). Mol. Cell. Biol., 22, 5157–5172.

  • Serrano M, Lin AW, McCurrach ME, Beach D and Lowe SW . (1997). Cell, 88, 593–602.

  • Shay JW . (1997). J. Cell. Physiol., 173, 266–270.

  • Smogorzewska A and de Lange T . (2002). EMBO J., 21, 4338–4348.

  • Stewart SA and Weinberg RA . (2002). Oncogene, 21, 627–630.

  • Vaziri H and Benchimol S . (1998). Curr. Biol., 8, 279–282.

  • Webley K, Bond JA, Jones CJ, Blaydes JP, Craig A, Hupp T and Wynford-Thomas D . (2000). Mol. Cell. Biol., 20, 2803–2808.

  • Xu D, Wang Q, Gruber A, Bjorkholm M, Chen Z, Zaid A, Selivanova G, Peterson C, Wiman KG and Pisa P . (2000). Oncogene, 19, 5123–5133.

  • Xu XC, Ro JY, Lee JS, Shin DM, Hong WK and Lotan R . (1994). Cancer Res., 54, 3580–3587.

Download references

Acknowledgements

We are grateful to Dr H Vaziri for his generous gift of the hTERT retroviral construct. We are grateful to Professors J Wyke and B Ozanne for critically reading the manuscript. AM was supported by the Glasgow Cancer School and White Lily Trust; PRH, KEP, JF and KG by Cancer Research UK and KH by Glasgow University.

Author information

Author notes

  1. Alessandra Muntoni

    Present address: Children's Medical Research Institute, 214 Hawkesbury Road, 2145, Westmead, NSW, Australia

Authors and Affiliations

  1. The Beatson Institute for Cancer Research, CRC Beatson Laboratories, Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1BD, UK

    Alessandra Muntoni, Janis Fleming, Katrina E Gordon, Keith Hunter, Fiona McGregor, E Kenneth Parkinson & Paul R Harrison

Authors
  1. Alessandra Muntoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Janis Fleming
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Katrina E Gordon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Keith Hunter
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fiona McGregor
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. E Kenneth Parkinson
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Paul R Harrison
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paul R Harrison.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Muntoni, A., Fleming, J., Gordon, K. et al. Senescing oral dysplasias are not immortalized by ectopic expression of hTERT alone without other molecular changes, such as loss of INK4A and/or retinoic acid receptor-β: but p53 mutations are not necessarily required. Oncogene 22, 7804–7808 (2003). https://doi.org/10.1038/sj.onc.1207085

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1207085

Keywords

This article is cited by

Search

Advanced search

Quick links