Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Bernhart, E; Damm, S; Heffeter, P; Wintersperger, A; Asslaber, M; Frank, S; Hammer, A; Strohmaier, H; DeVaney, T; Mrfka, M; Eder, H; Windpassinger, C; Ireson, CR; Mischel, PS; Berger, W; Sattler, W.
Silencing of protein kinase D2 induces glioma cell senescence via p53-dependent and -independent pathways.
Neuro Oncol. 2014; 16(7):933-945 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG


Autor/innen der Med Uni Graz:
Asslaber Martin
Bernhart Eva Maria
Damm Sabine
Devaney Trevor
Eder Hans
Frank Saša
Hammer Astrid
Mrfka Manuel
Sattler Wolfgang
Strohmaier Heimo
Windpassinger Christian
Wintersperger Andrea

Dimensions Citations:

Plum Analytics:
Number of Figures: 7
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Glioblastoma multiforme (GBM) is a highly aggressive tumor of the central nervous system with a dismal prognosis for affected patients. Aberrant protein kinase C (PKC) signaling has been implicated in gliomagenesis, and a member of the PKC-activated protein kinase D (PRKD) family, PRKD2, was identified as mediator of GBM growth in vitro and in vivo. The outcome of PRKD2 silencing and pharmacological inhibition on glioma cell proliferation was established with different glioma cell lines. Western blotting, senescence assays, co-immunoprecipitation, fluorescence activated cell sorting, quantitative PCR, and immunofluorescence microscopy were utilized to analyze downstream signaling. RNA-interference (21-mer siRNA) and pharmacological inhibition (CRT0066101) of PRKD2 profoundly inhibited proliferation of p53(wt) (U87MG, A172, and primary GBM2), and p53(mut) (GM133, T98G, U251, and primary Gli25) glioma cells. In a xenograft experiment, PRKD2 silencing significantly delayed tumor growth of U87MG cells. PRKD2 silencing in p53(wt) and p53(mut) cells was associated with typical hallmarks of senescence and cell cycle arrest in G1. Attenuated AKT/PKB phosphorylation in response to PRKD2 silencing was a common observation made in p53(wt) and p53(mut) GBM cells. PRKD2 knockdown in p53(wt) cells induced upregulation of p53, p21, and p27 expression, decreased phosphorylation of CDK2 and/or CDK4, hypophosphorylation of retinoblastoma protein (pRb), and reduced transcription of E2F1. In p53(mut) GM133 and primary Gli25 cells, PRKD2 silencing increased p27 and p15 and reduced E2F1 transcription but did not affect pRb phosphorylation. PRKD2 silencing induces glioma cell senescence via p53-dependent and -independent pathways.

Find related publications in this database (Keywords)
glioblastoma multiforme
protein kinase D2
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