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-beta: but p53 mutations are not necessarily required

Muntoni, A., Fleming, J., Gordon, K.E., Hunter, K., McGregor, F., Parkinson, E.K. and Harrison, P.R. (2003) 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-beta: but p53 mutations are not necessarily required. Oncogene, 22((49)), 7804 -7808. (doi: 10.1038/sj.onc.1207085)

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)-beta 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-beta 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-beta and p16INK4A expression) does not extend their lifespan, even though telomeres are lengthened.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Parkinson, Prof Eric and McGregor, Dr Fiona and Fleming, Ms Janice and Gordon, Mrs Karen and Hunter, Dr Keith and Harrison, Dr Paul
• Authors: Muntoni, A., Fleming, J., Gordon, K.E., Hunter, K., McGregor, F., Parkinson, E.K., and Harrison, P.R.
• Subjects: R Medicine > RK Dentistry
• College/School: College of Medical Veterinary and Life Sciences; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
• Journal Name: Oncogene
• ISSN: 0950-9232