| Literature DB >> 30355482 |
Alessandro Torgovnick1, Jan Michel Heger2, Vasiliki Liaki2, Jörg Isensee3, Anna Schmitt2, Gero Knittel2, Arina Riabinska2, Filippo Beleggia2, Lucie Laurien4, Uschi Leeser5, Christian Jüngst4, Florian Siedek6, Wenzel Vogel7, Niklas Klümper7, Hendrik Nolte4, Maike Wittersheim8, Lars Tharun8, Roberta Castiglione9, Marcus Krüger4, Astrid Schauss4, Sven Perner7, Manolis Pasparakis4, Reinhard Büttner10, Thorsten Persigehl6, Tim Hucho3, Grit Sophie Herter-Sprie2, Björn Schumacher11, Hans Christian Reinhardt12.
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.Entities:
Keywords: Cdkn1a; apoptosis; cancer; cancer protection; cell cycle arrest; mouse model; p21; p53; tumor suppressor
Mesh：
Substances：
Year: 2018 PMID： 30355482 DOI： 10.1016/j.celrep.2018.09.079
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423