Definition of Genetic Events Directing the Development of Distinct Types of Brain Tumors from Postnatal Neural Stem/Progenitor Cells.

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Definition of Genetic Events Directing the Development of Distinct Types of Brain Tumors from Postnatal Neural Stem/Progenitor Cells. / Hertwig, Falk; Meyer, Katharina; Braun, Sebastian; Ek, Sara; Spang, Rainer; Pfenninger, Cosima; Artner, Isabella; Prost, Gaelle; Chen, Xinbin; Biegel, Jaclyn A; Judkins, Alexander R; Englund, Elisabet; Nuber, Ulrike.

I: Cancer Research, Vol. 72, Nr. 13, 2012, s. 3381-3392.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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Hertwig, F, Meyer, K, Braun, S, Ek, S, Spang, R, Pfenninger, C, Artner, I, Prost, G, Chen, X, Biegel, JA, Judkins, AR, Englund, E & Nuber, U 2012, 'Definition of Genetic Events Directing the Development of Distinct Types of Brain Tumors from Postnatal Neural Stem/Progenitor Cells.', Cancer Research, vol. 72, nr. 13, s. 3381-3392. https://doi.org/10.1158/0008-5472.CAN-11-3525

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Author

Hertwig, Falk ; Meyer, Katharina ; Braun, Sebastian ; Ek, Sara ; Spang, Rainer ; Pfenninger, Cosima ; Artner, Isabella ; Prost, Gaelle ; Chen, Xinbin ; Biegel, Jaclyn A ; Judkins, Alexander R ; Englund, Elisabet ; Nuber, Ulrike. / Definition of Genetic Events Directing the Development of Distinct Types of Brain Tumors from Postnatal Neural Stem/Progenitor Cells. I: Cancer Research. 2012 ; Vol. 72, Nr. 13. s. 3381-3392.

RIS

TY - JOUR

T1 - Definition of Genetic Events Directing the Development of Distinct Types of Brain Tumors from Postnatal Neural Stem/Progenitor Cells.

AU - Hertwig, Falk

AU - Meyer, Katharina

AU - Braun, Sebastian

AU - Ek, Sara

AU - Spang, Rainer

AU - Pfenninger, Cosima

AU - Artner, Isabella

AU - Prost, Gaelle

AU - Chen, Xinbin

AU - Biegel, Jaclyn A

AU - Judkins, Alexander R

AU - Englund, Elisabet

AU - Nuber, Ulrike

N1 - The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Pathology, (Lund) (013030000), Stem Cell Center (013041110)

PY - 2012

Y1 - 2012

N2 - Although brain tumors are classified and treated based upon their histology, the molecular factors involved in the development of various tumor types remain unknown. In this study, we show that the type and order of genetic events directs the development of gliomas, central nervous system primitive neuroectodermal tumors, and atypical teratoid/rhabdoid-like tumors from postnatal mouse neural stem/progenitor cells (NSC/NPC). We found that the overexpression of specific genes led to the development of these three different brain tumors from NSC/NPCs, and manipulation of the order of genetic events was able to convert one established tumor type into another. In addition, loss of the nuclear chromatin-remodeling factor SMARCB1 in rhabdoid tumors led to increased phosphorylation of eIF2α, a central cytoplasmic unfolded protein response (UPR) component, suggesting a role for the UPR in these tumors. Consistent with this, application of the proteasome inhibitor bortezomib led to an increase in apoptosis of human cells with reduced SMARCB1 levels. Taken together, our findings indicate that the order of genetic events determines the phenotypes of brain tumors derived from a common precursor cell pool, and suggest that the UPR may represent a therapeutic target in atypical teratoid/rhabdoid tumors. Cancer Res; 72(13); 3381-92. ©2012 AACR.

AB - Although brain tumors are classified and treated based upon their histology, the molecular factors involved in the development of various tumor types remain unknown. In this study, we show that the type and order of genetic events directs the development of gliomas, central nervous system primitive neuroectodermal tumors, and atypical teratoid/rhabdoid-like tumors from postnatal mouse neural stem/progenitor cells (NSC/NPC). We found that the overexpression of specific genes led to the development of these three different brain tumors from NSC/NPCs, and manipulation of the order of genetic events was able to convert one established tumor type into another. In addition, loss of the nuclear chromatin-remodeling factor SMARCB1 in rhabdoid tumors led to increased phosphorylation of eIF2α, a central cytoplasmic unfolded protein response (UPR) component, suggesting a role for the UPR in these tumors. Consistent with this, application of the proteasome inhibitor bortezomib led to an increase in apoptosis of human cells with reduced SMARCB1 levels. Taken together, our findings indicate that the order of genetic events determines the phenotypes of brain tumors derived from a common precursor cell pool, and suggest that the UPR may represent a therapeutic target in atypical teratoid/rhabdoid tumors. Cancer Res; 72(13); 3381-92. ©2012 AACR.

U2 - 10.1158/0008-5472.CAN-11-3525

DO - 10.1158/0008-5472.CAN-11-3525

M3 - Article

VL - 72

SP - 3381

EP - 3392

JO - Cancer research. Supplement

T2 - Cancer research. Supplement

JF - Cancer research. Supplement

SN - 1538-7445

IS - 13

ER -