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Telomere dysfunction suppresses spontaneous tumorigenesis in vivo by initiating p53‐dependent cellular senescence
Author(s) -
CosmeBlanco Wilfredo,
Shen MeiFeng,
Lazar Alexander J F,
Pathak Sen,
Lozano Guillermina,
Multani Asha S,
Chang Sandy
Publication year - 2007
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400937
Subject(s) - senescence , telomere , carcinogenesis , biology , microbiology and biotechnology , cell cycle checkpoint , telomerase , apoptosis , in vivo , cell cycle , cancer research , dna damage , genetics , cancer , gene , dna
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‐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.