Increased gene dosage ofInk4a/Arfresults in cancer resistance and normal aging
| Autor: | Alejo Efeyan, Juana M. Flores, Juan Martín-Caballero, Ander Matheu, Peter Klatt, Cristina Pantoja, Manuel Serrano, Luis M. Criado |
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| Rok vydání: | 2004 |
| Předmět: |
Male
Heterozygote Cell Survival 9 10-Dimethyl-1 2-benzanthracene Transgene Gene Dosage Mice Transgenic Biology Gene dosage law.invention Mice law Genetics Animals Humans Genes Tumor Suppressor neoplasms Gene Cells Cultured Cellular Senescence Cyclin-Dependent Kinase Inhibitor p16 integumentary system Homozygote Heterozygote advantage Neoplasms Experimental Fibroblasts Embryo Mammalian Research Papers Phenotype Molecular biology In vitro Mice Inbred C57BL Cell Transformation Neoplastic embryonic structures Carcinogens Cancer research Suppressor Female biological phenomena cell phenomena and immunity Cell aging Developmental Biology |
| Zdroj: | Genes & Development. 18:2736-2746 |
| ISSN: | 1549-5477 0890-9369 |
| DOI: | 10.1101/gad.310304 |
| Popis: | Mammalian genes frequently present allelic variants that differ in their expression levels and that, in the case of tumor suppressor genes, can be of relevance for cancer susceptibility and aging. We report here the characterization of a novel mouse model with increased activity for the Ink4a and Arf tumor suppressors. We have generated a “superInk4a/Arf” mouse strain carrying a transgenic copy of the entireInk4a/Arflocus. Cells derived from superInk4a/Arfmice have increased resistance to in vitro immortalization and oncogenic transformation. Importantly, superInk4a/Arfmice manifest higher resistance to cancer compared to normal, nontransgenic, mice. Finally, superInk4a/Arfmice have normal aging and lifespan. Together, these results indicate that modest increases in the activity of theInk4a/Arftumor suppressor result in a beneficial cancer-resistant phenotype without affecting normal viability or aging. |
| Databáze: | OpenAIRE |
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