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http://doi.org/10.25358/openscience-218
Autoren: | Vewinger, Nadine Huprich, Sabrina Seidmann, Larissa Russo, Alexandra Alt, Francesca Bender, Hannah Sommer, Clemens Samuel, David Lehmann, Nadine Backes, Nora Roth, Lea Harter, Patrick N. Filipski, Katharina Faber, Jörg Paret, Claudia |
Titel: | IGF1R is a potential new therapeutic target for HGNET-BCOR brain tumor patients |
Online-Publikationsdatum: | 7-Nov-2019 |
Erscheinungsdatum: | 2019 |
Sprache des Dokuments: | Englisch |
Zusammenfassung/Abstract: | (1) Background: The high-grade neuroepithelial tumor of the central nervous system with BCOR alteration (HGNET-BCOR) is a highly malignant tumor. Preclinical models and molecular targets are urgently required for this cancer. Previous data suggest a potential role of insulin-like growth factor (IGF) signaling in HGNET-BCOR. (2) Methods: The primary HGNET-BCOR cells PhKh1 were characterized by western blot, copy number variation, and methylation analysis and by electron microscopy. The expression of IGF2 and IGF1R was assessed by qRT-PCR. The effect of chemotherapeutics and IGF1R inhibitors on PhKh1 proliferation was tested. The phosphorylation of IGF1R and downstream molecules was assessed by western blot. (3) Results: Phkh1 cells showed a DNA methylation profile compatible with the DNA methylation class “HGNET-BCOR” and morphologic features of cellular cannibalism. IGF2 and IGF1R were highly expressed by three HGNET-BCOR tumor samples and PhKh1 cells. PhKh1 cells were particularly sensitive to vincristine, vinblastine, actinomycin D (IC50 < 10 nM for all drugs), and ceritinib (IC50 = 310 nM). Ceritinib was able to abrogate the proliferation of PhKh1 cells and blocked the phosphorylation of IGF1R and AKT. (4) Conclusion: IGF1R is as an attractive target for the development of new therapy protocols for HGNET-BCOR patients, which may include ceritinib and vinblastine. |
DDC-Sachgruppe: | 610 Medizin 610 Medical sciences |
Veröffentlichende Institution: | Johannes Gutenberg-Universität Mainz |
Organisationseinheit: | FB 04 Medizin |
Veröffentlichungsort: | Mainz |
ROR: | https://ror.org/023b0x485 |
DOI: | http://doi.org/10.25358/openscience-218 |
URN: | urn:nbn:de:hebis:77-publ-594015 |
Version: | Published version |
Publikationstyp: | Zeitschriftenaufsatz |
Nutzungsrechte: | CC BY |
Informationen zu den Nutzungsrechten: | https://creativecommons.org/licenses/by/4.0/ |
Zeitschrift: | International journal of molecular sciences 20 12 |
Seitenzahl oder Artikelnummer: | Art. 3027 |
Verlag: | Molecular Diversity Preservation International |
Verlagsort: | Basel |
Erscheinungsdatum: | 2019 |
ISSN: | 1422-0067 1661-6596 |
URL der Originalveröffentlichung: | http://dx.doi.org/10.3390/ijms20123027 |
DOI der Originalveröffentlichung: | 10.3390/ijms20123027 |
Enthalten in den Sammlungen: | JGU-Publikationen |
Dateien zu dieser Ressource:
Datei | Beschreibung | Größe | Format | ||
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59401.pdf | 1.75 MB | Adobe PDF | Öffnen/Anzeigen |