The Cdkn1aSUPER Mouse as a Tool to Study p53-Mediated Tumor Suppression.
Cell Rep
; 25(4): 1027-1039.e6, 2018 10 23.
Article
em En
| MEDLINE
| ID: mdl-30355482
ABSTRACT
Cdkn1a, which encodes p21, functions as a major route for p53-mediated cell-cycle arrest. However, the consequence of Cdkn1a gene dosage on tumor suppression has not been systematically investigated. Here, we employed BAC transgenesis to generate a Cdkn1aSUPER mouse, which harbors an additional Cdkn1a allele within its natural genomic context. We show that these mice display enhanced cell-cycle arrest and reduced apoptosis in response to genotoxic stress. Furthermore, using a chemically induced skin cancer model and an autochthonous Kras-driven lung adenocarcinoma model, we show that Cdkn1aSUPER mice display a cancer protection phenotype that is indistinguishable from that observed in Tp53SUPER animals. Moreover, we demonstrate that Tp53 and Cdkn1a cooperate in mediating cancer resistance, using a chemically induced fibrosarcoma model. Overall, our Cdkn1aSUPER allele enabled us to assess the contribution of Cdkn1a to Tp53-mediated tumor suppression.
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Base de dados:
MEDLINE
Assunto principal:
Proteína Supressora de Tumor p53
/
Inibidor de Quinase Dependente de Ciclina p21
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article