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Verfasst von:Berger, Benjamin [VerfasserIn]   i
 Capper, David [VerfasserIn]   i
 Lemke, Dieter [VerfasserIn]   i
 Pfenning, Philipp-Niclas [VerfasserIn]   i
 Platten, Michael [VerfasserIn]   i
 Weller, Michael [VerfasserIn]   i
 Deimling, Andreas von [VerfasserIn]   i
 Wick, Wolfgang [VerfasserIn]   i
 Weiler, Markus [VerfasserIn]   i
Titel:Defective p53 antiangiogenic signaling in glioblastoma
Verf.angabe:Benjamin Berger, David Capper, Dieter Lemke, Philipp-Niclas Pfenning, Michael Platten, Michael Weller, Andreas von Deimling, Wolfgang Wick, and Markus Weiler
E-Jahr:2010
Jahr:March 31, 2010
Umfang:14 S.
Fussnoten:Gesehen am 18.01.2023
Titel Quelle:Enthalten in: Neuro-Oncology
Ort Quelle:Oxford : Oxford Univ. Press, 1999
Jahr Quelle:2010
Band/Heft Quelle:12(2010), 9, Seite 894-907
ISSN Quelle:1523-5866
Abstract:Previous findings suggest an angiogenesis-regulating function of the p53 tumor suppressor protein in various malignancies. With several antiangiogenic agents entering the clinic, we assessed the value of the TP53 status in predicting angiogenesis in glioblastoma in vivo and examined underlying angiogenic-signaling pathways in vitro. We identified 26 TP53 wild-type and 9 TP53 mutated treatment-naïve, primary, isocitrate dehydrogenase 1 (IDH1) wild-type glioblastoma specimens by sequence analysis and quantified vascularization. P53 responsiveness of the angiogenesis-related target genes, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), thrombospondin 1 (TSP-1), brain-specific angiogenesis inhibitor 1 (BAI1), and collagen prolyl-4-hydroxylase alpha 2 (P4HA2), was evaluated by (i) overexpression of wild-type p53 in homozygously TP53-deleted LN-308 cells; (ii) shRNA-mediated p53 knockdown in the TP53 wild-type LNT-229 cells; and (iii) chemical induction of wild-type p53 expression in LNT-229 cells by camptothecin. Irrespective of the TP53 status, vascularization did not differ significantly between the two groups of glioblastoma specimens. Of all target genes, only P4HA2 mRNA was upregulated through wild-type p53. As opposed to several nonglial tumors, in glioblastoma cells, p53-mediated transcriptional induction of P4HA2 mRNA neither resulted in increased levels of P4HA2 protein or antiangiogenic endostatin nor did it influence endothelial cell sprouting, viability, or transmigration in vitro. Moreover, p53-uncoupled stable overexpression of P4HA2 in LN-308 cells did not affect endothelial cell viability. These data challenge the view of p53 as an angiogenesis-regulator in glioblastoma in that relevant signaling pathways are silenced, potentially contributing to the angiogenic switch during malignant progression.
DOI:doi:10.1093/neuonc/noq051
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

DOI: https://doi.org/10.1093/neuonc/noq051
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Brain Neoplasms
 Enzyme-Linked Immunosorbent Assay
 Gene Expression
 Gene Expression Regulation, Neoplastic
 Gene Knockdown Techniques
 Glioblastoma
 Humans
 Immunoblotting
 Neovascularization, Pathologic
 Promoter Regions, Genetic
 Reverse Transcriptase Polymerase Chain Reaction
 Signal Transduction
 Transfection
 Tumor Suppressor Protein p53
K10plus-PPN:1831401916
Verknüpfungen:→ Zeitschrift

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