Senescence induction in renal carcinoma cells by Nutlin-3: a potential therapeutic strategy based on MDM2 antagonism
| Autor: | Radoslaw Polanski, Mark T. Boyd, Jeremy P. Blaydes, K F Parsons, Nikolina Vlatkovic, Anna Phillips, Carlos P. Rubbi, Aidan P. Noon |
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| Rok vydání: | 2014 |
| Předmět: |
Senescence
Cancer Research medicine.medical_treatment Antineoplastic Agents urologic and male genital diseases Piperazines Targeted therapy law.invention chemistry.chemical_compound Renal cell carcinoma law Cell Line Tumor medicine Humans RNA Messenger neoplasms Carcinoma Renal Cell Cellular Senescence Cell Proliferation biology Imidazoles Proto-Oncogene Proteins c-mdm2 Nutlin medicine.disease female genital diseases and pregnancy complications Kidney Neoplasms Gene Expression Regulation Neoplastic Oncology chemistry Apoptosis biology.protein Cancer research Mdm2 Suppressor Growth inhibition Tumor Suppressor Protein p53 |
| Zdroj: | Cancer Letters |
| ISSN: | 1872-7980 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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