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Status: Bibliographieeintrag

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Verfasst von:Reuss, David [VerfasserIn]   i
 Mucha, Jana [VerfasserIn]   i
 Hagenlocher, Christian [VerfasserIn]   i
 Ehemann, Volker [VerfasserIn]   i
 Kluwe, Lan [VerfasserIn]   i
 Mautner, Victor [VerfasserIn]   i
 Deimling, Andreas von [VerfasserIn]   i
Titel:Sensitivity of malignant peripheral nerve sheath tumor cells to TRAIL is augmented by loss of NF1 through modulation of MYC/MAD and is potentiated by curcumin through induction of ROS
Verf.angabe:David E. Reuss, Jana Mucha, Christian Hagenlocher, Volker Ehemann, Lan Kluwe, Victor Mautner, Andreas von Deimling
E-Jahr:2013
Jahr:February 21, 2013
Umfang:10 S.
Fussnoten:Gesehen am 04.01.2022
Titel Quelle:Enthalten in: PLOS ONE
Ort Quelle:San Francisco, California, US : PLOS, 2006
Jahr Quelle:2013
Band/Heft Quelle:8(2013), 2, Artikel-ID e57152, Seite 1-10
ISSN Quelle:1932-6203
Abstract:Malignant peripheral nerve sheath tumor (MPNST) is a rare aggressive form of sarcoma often associated with the tumor syndrome neurofibromatosis type 1 (NF1). We investigated the effects of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) on NF1 associated MPNST and determinants of TRAIL sensitivity. MPNST cell lines with complete neurofibromin deficiency were sensitive to apoptotic cell death induced by TRAIL whereas MPNST cells with retained neurofibromin expression or normal human Schwann cells were resistant. Increased sensitivity to TRAIL was associated with overexpression of death receptors, especially DR5. Re-expression of the GAP related domain of neurofibromin (NF1-GRD) suppressed DR5 expression and decreased sensitivity to TRAIL. We show that death receptor expression and TRAIL sensitivity critically depend on c-MYC and that c-MYC amounts are increased by MEK/ERK and PI3K/AKT signalling pathways which are suppressed by neurofibromin. Furthermore PI3K/AKT signalling strongly suppresses the MYC-antagonist MAD1 which significantly contributes to TRAIL sensitivity. Re-expression of the NF1-GRD decreased c-MYC and increased MAD1 amounts suggesting that neurofibromin influences TRAIL sensitivity at least in part by modulating the MYC/MAX/MAD network. The phytochemical curcumin further increased the sensitivity of neurofibromin deficient MPNST cells to TRAIL. This was presumably mediated by ROS, as it correlated with increased ROS production, was blocked by N-acetylcysteine and mimicked by exogenous ROS.
DOI:doi:10.1371/journal.pone.0057152
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.

Volltext ; Verlag: https://doi.org/10.1371/journal.pone.0057152
 Volltext: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0057152
 DOI: https://doi.org/10.1371/journal.pone.0057152
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Apoptosis
 Flow cytometry
 Immunoblotting
 Malignant tumors
 Neurofibromatosis type 1
 Schwann cells
 Small interfering RNA
 Transfection
K10plus-PPN:1784527955
Verknüpfungen:→ Zeitschrift

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