Telomere dysfunction suppresses spontaneous tumorigenesis in vivo by initiating p53‐dependent cellular senescence
Open Access
- 30 March 2007
- journal article
- Published by Springer Nature in EMBO Reports
- Vol. 8 (5) , 497-503
- https://doi.org/10.1038/sj.embor.7400937
Abstract
Dysfunctional telomeres induce p53‐dependent cellular senescence and apoptosis, but it is not known which function is more important for tumour suppression in vivo. We used the p53R172P knock‐in mouse, which is unable to induce apoptosis but retains intact cell‐cycle arrest and cellular senescence pathways, to show that spontaneous tumorigenesis is potently repressed in Terc−/−p53R172P mice. Tumour suppression is accompanied by global induction of p53, p21 and the senescence marker senescence‐associated‐β‐galactosidase. By contrast, cellular senescence was unable to suppress chemically induced skin carcinomas. These results indicate that suppression of spontaneous tumorigenesis by dysfunctional telomeres requires the activation of the p53‐dependent cellular senescence pathway.Keywords
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