TY  - JOUR
A1  - Raab, Monika
A1  - Kappel, Sven
A1  - Krämer, Andrea
A1  - Sanhaji, Mourad
A1  - Matthess, Yves
A1  - Kurunci-Csacsko, Elisabeth
A1  - Calzada-Wack, Julia
A1  - Rathkolb, Birgit
A1  - Rozman, Jan
A1  - Adler, Thure
A1  - Busch, Dirk H.
A1  - Esposito, Irene
A1  - Fuchs, Helmut
A1  - Gailus-Durner, Valérie
A1  - Klingenspor, Martin
A1  - Wolf, Eckhard
A1  - Sänger, Nicole
A1  - Prinz, Florian
A1  - Hrabé de Angelis, Martin
A1  - Seibler, Jost
A1  - Yuan, Juping
A1  - Bergmann, Martin
A1  - Knecht, Rainald
A1  - Kreft, Bertolt
A1  - Strebhardt, Klaus
T1  - Toxicity modelling of Plk1-targeted therapies in genetically engineered mice and cultured primary mammalian cells
T2  - Nature Communications
N2  - High attrition rates of novel anti-cancer drugs highlight the need for improved models to predict toxicity. Although polo-like kinase 1 (Plk1) inhibitors are attractive candidates for drug development, the role of Plk1 in primary cells remains widely unexplored. Therefore, we evaluated the utility of an RNA interference-based model to assess responses to an inducible knockdown (iKD) of Plk1 in adult mice. Here we show that Plk1 silencing can be achieved in several organs, although adverse events are rare. We compared responses in Plk1-iKD mice with those in primary cells kept under controlled culture conditions. In contrast to the addiction of many cancer cell lines to the non-oncogene Plk1, the primary cells' proliferation, spindle assembly and apoptosis exhibit only a low dependency on Plk1. Responses to Plk1-depletion, both in cultured primary cells and in our iKD-mouse model, correspond well and thus provide the basis for using validated iKD mice in predicting responses to therapeutic interventions.
Y1  - 2011
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/28940
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-289400
SN  - 2041-1723
N1  - License: This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
VL  - 2
IS  - Article number: 395
PB  - Nature Publishing Group
CY  - London
ER  -