Senescence induction in renal carcinoma cells by Nutlin-3: a potential therapeutic strategy based on MDM2 antagonism

Polanski, Radoslaw, Noon, Aidan P, Blaydes, Jeremy, Phillips, Anna, Rubbi, Carlos P, Parsons, Keith, Vlatkovic, Nikolina ORCID: 0000-0003-3003-794X and Boyd, Mark T ORCID: 0000-0002-2336-2106 (2014) Senescence induction in renal carcinoma cells by Nutlin-3: a potential therapeutic strategy based on MDM2 antagonism. Cancer Letters, 353 (2). pp. 211-219.

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Abstract

Although the role of p53 as a tumour suppressor in renal cell carcinoma (RCC) is unclear, our recent analysis suggests that increased wild-type p53 protein expression is associated with poor outcome. A growing body of evidence also suggests that p53 expression and increased co-expression of MDM2 are linked with poor prognosis in RCC. We have therefore examined whether an MDM2 antagonist; Nutlin-3, might rescue/increase p53 expression and induce growth inhibition or apoptosis in RCC cells that retain wild-type p53. We show that inhibition of p53 suppression by MDM2 in RCC cells promotes growth arrest and p53-dependent senescence – phenotypes known to mediate p53 tumour suppression in vivo. We propose that future investigations of therapeutic strategies for RCC should incorporate MDM2 antagonism as part of strategies aimed at rescuing/augmenting p53 tumour suppressor function.

Item Type:	Article
Uncontrolled Keywords:	Renal cell carcinoma, p53, MDM2, Nutlin-3, Senescence, Targeted therapy
Depositing User:	Symplectic Admin
Date Deposited:	15 Jul 2016 13:30
Last Modified:	19 Jan 2023 07:33
DOI:	10.1016/j.canlet.2014.07.024
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3002362