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

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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. Access through your institution Buy or subscribe This is a preview of subscription


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ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS REPROGRAMMING OF THE ESOPHAGEAL SQUAMOUS


CARCINOMA EPIGENOME BY SOX2 PROMOTES ADAR1 DEPENDENCE Article 10 May 2021 A NON-GENETIC SWITCH TRIGGERS ALTERNATIVE TELOMERE LENGTHENING AND CELLULAR IMMORTALIZATION IN ATRX DEFICIENT CELLS


Article Open access 20 February 2023 SELF-SUSTAINING LONG-TERM 3D EPITHELIOID CULTURES REVEAL DRIVERS OF CLONAL EXPANSION IN ESOPHAGEAL EPITHELIUM Article Open access 23 September 2024


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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 * Alessandra Muntoni Present address: Children's Medical Research


Institute, 214 Hawkesbury Road, 2145, Westmead, NSW, Australia AUTHORS AND AFFILIATIONS * 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 * Alessandra Muntoni


View author publications You can also search for this author inPubMed Google Scholar * Janis Fleming View author publications You can also search for this author inPubMed Google Scholar *


Katrina E Gordon View author publications You can also search for this author inPubMed Google Scholar * Keith Hunter View author publications You can also search for this author inPubMed 


Google Scholar * Fiona McGregor View author publications You can also search for this author inPubMed Google Scholar * E Kenneth Parkinson View author publications You can also search for


this author inPubMed Google Scholar * Paul R Harrison View author publications You can also search for this author inPubMed 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: 07 January 2003 * Revised: 16 July 2003 * Accepted: 05 August 2003 * Published: 30 October 2003 * Issue


Date: 30 October 2003 * DOI: https://doi.org/10.1038/sj.onc.1207085 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry,


a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * head and neck cancer *


preneoplasia * immortalization * RAR-_β_ * INK4A * telomerase