title: Ets Factors Regulate Neural Stem Cell Depletion and Gliogenesis in Ras Pathway Glioma.
abstract: As the list of putative driver mutations in glioma grows, we are just beginning to elucidate the effects of dysregulated developmental signaling pathways on the transformation of neural cells. We have employed a postnatal, mosaic, autochthonous glioma model that captures the first hours and days of gliomagenesis in more resolution than conventional genetically engineered mouse models of cancer. We provide evidence that disruption of the Nf1-Ras pathway in the ventricular zone at multiple signaling nodes uniformly results in rapid neural stem cell depletion, progenitor hyperproliferation, and gliogenic lineage restriction. Abolishing Ets subfamily activity, which is upregulated downstream of Ras, rescues these phenotypes and blocks glioma initiation. Thus, the Nf1-Ras-Ets axis might be one of the select molecular pathways that are perturbed for initiation and maintenance in glioma.
authors.affiliation: Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. Electronic address: joshua.breunig@cshs.org.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Breunig
authors.affiliation: Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Rachelle
authors.initials: R
authors.lastname: Levy
authors.affiliation: Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: C Danielle
authors.initials: CD
authors.lastname: Antonuk
authors.affiliation: Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Molina
authors.affiliation: Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Dutra-Clarke
authors.affiliation: Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Hannah
authors.initials: H
authors.lastname: Park
authors.affiliation: Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Aslam Abbasi
authors.initials: AA
authors.lastname: Akhtar
authors.affiliation: Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Gi Bum
authors.initials: GB
authors.lastname: Kim
authors.affiliation: Department of Genomic Medicine, Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Serguei I
authors.initials: SI
authors.lastname: Bannykh
authors.affiliation: Department of Genomic Medicine, Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Roel G W
authors.initials: RG
authors.lastname: Verhaak
authors.affiliation: Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Moise
authors.initials: M
authors.lastname: Danielpour
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D017930:Genes, Reporter; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D051379:Mice; D018613:Microscopy, Confocal; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D025542:Neurofibromin 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C513242:Etv5 protein, mouse; D025542:Neurofibromin 1; D050783:Proto-Oncogene Proteins c-ets; D034741:RNA, Small Interfering; D014157:Transcription Factors; D018631:ras Proteins