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EMBO reports 8, 5, 497–503 (2007)
doi:10.1038/sj.embor.7400937
AOP Published online: 30 March 2007
Telomere dysfunction suppresses spontaneous tumorigenesis in vivo by initiating p53-dependent cellular senescence
Wilfredo Cosme-Blanco1, Mei-Feng Shen1, Alexander J F Lazar2, Sen Pathak1, Guillermina Lozano1, Asha S Multani1 & Sandy Chang1, 3
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1
Department of Cancer Genetics, The MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA
2
Departments of Pathology and Dermatology, The MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA
3
Department of Hematopathology, The MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA
To whom correspondence should be addressed
Sandy Chang
Tel: +1 713 834 6361; Fax: +1 713 834 6319; E-mail: schang@mdanderson.org
Received 13 November 2006; Accepted 6 February 2007; Published online 30 March 2007.
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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- -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.
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