Telomere dysfunction suppresses spontaneous tumorigenesis in vivo by initiating p53‐dependent cellular senescence
| Autor: | Wilfredo Cosme-Blanco, Guillermina Lozano, Alexander J. Lazar, Sen Pathak, Sandy Chang, Asha S. Multani, Mei Feng Shen |
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| Rok vydání: | 2007 |
| Předmět: |
Senescence
Skin Neoplasms DNA damage 9 10-Dimethyl-1 2-benzanthracene Scientific Report Apoptosis Biology medicine.disease_cause Biochemistry Mice In vivo Genetics medicine Animals Molecular Biology Cellular Senescence Papilloma Fibroblasts Telomere Embryo Mammalian Cell biology Cancer research Tumor Suppressor Protein p53 Carcinogenesis Cell aging Function (biology) |
| Zdroj: | EMBO reports. 8:497-503 |
| ISSN: | 1469-3178 1469-221X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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