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EMBO Rep. 2007 May;8(5):497-503. Epub 2007 Mar 30.

Telomere dysfunction suppresses spontaneous tumorigenesis in vivo by initiating p53-dependent cellular senescence.

Author information

1
Department of Cancer Genetics, The MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.

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 p53 ( R172P ) 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 -/- p53 ( R172P ) mice. Tumour suppression is accompanied by global induction of p53, p21 and the senescence marker senescence-associated-beta-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.

PMID:
17396137
PMCID:
PMC1866197
DOI:
10.1038/sj.embor.7400937
[Indexed for MEDLINE]
Free PMC Article

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