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Raab, M.* ; Kappel, S.* ; Krämer, A.* ; Sanhaji, M.* ; Matthess, Y.* ; Kurunci-Csacsko, E.* ; Calzada-Wack, J. ; Rathkolb, B. ; Rozman, J. ; Adler, T. ; Busch, D.H.* ; Esposito, I. ; Fuchs, H. ; Gailus-Durner, V. ; Klingenspor, M.* ; Wolf, E.* ; Sänger, N.* ; Prinz, F.* ; Hrabě de Angelis, M. ; Seibler, J.* ; Yuan, J.* ; Bergmann, M.* ; Knecht, R.* ; Kreft, B.* ; Strebhardt, K.*

Toxicity modelling of Plk1-targeted therapies in genetically engineered mice and cultured primary mammalian cells.

Nat. Commun. 2:395 (2011)
Publ. Version/Full Text Volltext DOI PMC
Open Access Gold
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords POLO-LIKE KINASE; SPINDLE-ASSEMBLY CHECKPOINT; INDUCIBLE SHRNA EXPRESSION; INHIBITS TUMOR-GROWTH; BREAST-CANCER; GENE KNOCKDOWN; BI 2536; PLK1; MOUSE; SPERMATOGENESIS
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 2, Issue: 1, Pages: , Article Number: 395 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Experimental Genetics (IEG)
Institute of Pathology (PATH)