Torgovnick, Alessandro, Heger, Jan Michel, Liaki, Vasiliki, Isensee, Joerg ORCID: 0000-0002-3390-0051, Schmitt, Anna, Knittel, Gero, Riabinska, Arina, Beleggia, Filippo ORCID: 0000-0003-0234-7094, Laurien, Lucie, Leeser, Uschi, Juengst, Christian, Siedek, Florian, Vogel, Wenzel, Kluemper, Niklas, Nolte, Hendrik, Wittersheim, Maike, Tharun, Lars, Castiglione, Roberta ORCID: 0000-0002-9828-4405, Krueger, Marcus, Schauss, Astrid, Perner, Sven, Pasparakis, Manolis ORCID: 0000-0002-9870-0966, Buettner, Reinhard, Persigehl, Thorsten, Hucho, Tim, Herter-Sprie, Grit Sophie, Schumacher, Bjoern and Reinhardt, Hans Christian (2018). The Cdkn1a(SuPER) Mouse as a Tool to Study p53-Mediated Tumor Suppression. Cell Reports, 25 (4). S. 1027 - 1046. CAMBRIDGE: CELL PRESS. ISSN 2211-1247

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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 Cdkn1a(SUPER) 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 Krasdriven lung adenocarcinoma model, we show that Cdkn1a(SUPER) mice display a cancer protection phenotype that is indistinguishable from that observed in Tp53 suPER animals. Moreover, we demonstrate that Tp53 and Cdkn1a cooperate in mediating cancer resistance, using a chemically induced fibrosarcoma model. Overall, our Cdkn1a(SUPER )allele enabled us to assess the contribution of Cdkn1a to Tp53-mediated tumor suppression.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Torgovnick, AlessandroUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heger, Jan MichelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liaki, VasilikiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Isensee, JoergUNSPECIFIEDorcid.org/0000-0002-3390-0051UNSPECIFIED
Schmitt, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Knittel, GeroUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Riabinska, ArinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beleggia, FilippoUNSPECIFIEDorcid.org/0000-0003-0234-7094UNSPECIFIED
Laurien, LucieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leeser, UschiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Juengst, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Siedek, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vogel, WenzelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kluemper, NiklasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nolte, HendrikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wittersheim, MaikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tharun, LarsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Castiglione, RobertaUNSPECIFIEDorcid.org/0000-0002-9828-4405UNSPECIFIED
Krueger, MarcusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schauss, AstridUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Perner, SvenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pasparakis, ManolisUNSPECIFIEDorcid.org/0000-0002-9870-0966UNSPECIFIED
Buettner, ReinhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Persigehl, ThorstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hucho, TimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herter-Sprie, Grit SophieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schumacher, BjoernUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reinhardt, Hans ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-169079
DOI: 10.1016/j.celrep.2018.09.079
Journal or Publication Title: Cell Reports
Volume: 25
Number: 4
Page Range: S. 1027 - 1046
Date: 2018
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 2211-1247
Language: English
Faculty: Faculty of Mathematics and Natural Sciences
Divisions: Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
DNA-DAMAGE RESPONSES; P53 GENE; CANCER; P21; MICE; RAS; RESTORATION; DEFICIENCY; SENESCENCE; ABSENCEMultiple languages
Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/16907

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