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

Wilfredo Cosme-Blanco; Mei Feng Shen; Alexander J.F. Lazar; Sen Pathak; Guillermina Lozano; Asha S. Multani; Sandy Chang

doi:10.1038/sj.embor.7400937

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

Wilfredo Cosme-Blanco, Mei Feng Shen, Alexander J.F. Lazar, Sen Pathak, Guillermina Lozano, Asha S. Multani, Sandy Chang

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167 Scopus citations

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-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.

Original language	English (US)
Pages (from-to)	497-503
Number of pages	7
Journal	EMBO reports
Volume	8
Issue number	5
DOIs	https://doi.org/10.1038/sj.embor.7400937
State	Published - May 2007

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Genetics

MD Anderson CCSG core facilities

Genetically Engineered Mouse Facility

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title = "Telomere dysfunction suppresses spontaneous tumorigenesis in vivo by initiating p53-dependent cellular senescence",

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.",

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AU - Cosme-Blanco, Wilfredo

AU - Shen, Mei Feng

AU - Lazar, Alexander J.F.

AU - Pathak, Sen

AU - Lozano, Guillermina

AU - Multani, Asha S.

AU - Chang, Sandy

PY - 2007/5

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N2 - 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.

AB - 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.

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

Abstract

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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