Definition of Genetic Events Directing the Development of Distinct Types of Brain Tumors from Postnatal Neural Stem/Progenitor Cells.
(2012) In Cancer Research 72(13). p.3381-3392- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2859180
- author
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Cancer Research
- volume
- 72
- issue
- 13
- pages
- 3381 - 3392
- publisher
- American Association for Cancer Research Inc.
- external identifiers
-
- wos:000307350700027
- pmid:22719073
- scopus:84863584862
- pmid:22719073
- ISSN
- 1538-7445
- DOI
- 10.1158/0008-5472.CAN-11-3525
- language
- English
- LU publication?
- yes
- additional info
- 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)
- id
- 625f8489-9746-4673-a4e0-c6c6309f8acf (old id 2859180)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/22719073?dopt=Abstract
- date added to LUP
- 2016-04-04 09:45:32
- date last changed
- 2022-02-21 02:18:54
@article{625f8489-9746-4673-a4e0-c6c6309f8acf, abstract = {{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.}}, author = {{Hertwig, Falk and Meyer, Katharina and Braun, Sebastian and Ek, Sara and Spang, Rainer and Pfenninger, Cosima and Artner, Isabella and Prost, Gaelle and Chen, Xinbin and Biegel, Jaclyn A and Judkins, Alexander R and Englund, Elisabet and Nuber, Ulrike}}, issn = {{1538-7445}}, language = {{eng}}, number = {{13}}, pages = {{3381--3392}}, publisher = {{American Association for Cancer Research Inc.}}, series = {{Cancer Research}}, title = {{Definition of Genetic Events Directing the Development of Distinct Types of Brain Tumors from Postnatal Neural Stem/Progenitor Cells.}}, url = {{http://dx.doi.org/10.1158/0008-5472.CAN-11-3525}}, doi = {{10.1158/0008-5472.CAN-11-3525}}, volume = {{72}}, year = {{2012}}, }