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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)
Verlagsversion Volltext DOI PMC
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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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter POLO-LIKE KINASE; SPINDLE-ASSEMBLY CHECKPOINT; INDUCIBLE SHRNA EXPRESSION; INHIBITS TUMOR-GROWTH; BREAST-CANCER; GENE KNOCKDOWN; BI 2536; PLK1; MOUSE; SPERMATOGENESIS
Sprache
Veröffentlichungsjahr 2011
HGF-Berichtsjahr 2011
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 2, Heft: 1, Seiten: , Artikelnummer: 395 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Experimental Genetics (IEG)
Institute of Pathology (PATH)
POF Topic(s) 30201 - Metabolic Health
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Genetics and Epidemiology
Enabling and Novel Technologies
PSP-Element(e) G-500600-003
G-500600-001
G-500300-001
PubMed ID 21772266
DOI 10.1038/ncomms1395
WOS ID 000294805300022
Scopus ID 79960580428
Erfassungsdatum 2011-09-12
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