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Stabilization of HIF-1α and HIF-2α, up-regulation of MYCC and accumulation of stabilized p53 constitute hallmarks of CNS-PNET animal model
- Source :
- PLoS ONE, Vol 12, Iss 3, p e0173106 (2017), PLoS ONE
- Publication Year :
- 2017
- Publisher :
- Public Library of Science (PLoS), 2017.
-
Abstract
- Recently, we described a new animal model of CNS primitive neuroectodermal tumors (CNS-PNET), which was generated by orthotopic transplantation of human Radial Glial (RG) cells into NOD-SCID mice’s brain sub-ventricular zone. In the current study we conducted comprehensive RNA-Seq analyses to gain insights on the mechanisms underlying tumorigenesis in this mouse model of CNS-PNET. Here we show that the RNA-Seq profiles derived from these tumors cluster with those reported for patients’ PNETs. Moreover, we found that (i) stabilization of HIF-1α and HIF-2α, which are involved in mediation of the hypoxic responses in the majority of cell types, (ii) up-regulation of MYCC, a key onco-protein whose dysregulation occurs in ~70% of human tumors, and (iii) accumulation of stabilized p53, which is commonly altered in human cancers, constitute hallmarks of our tumor model, and might represent the basis for CNS-PNET tumorigenesis in this model. We discuss the possibility that these three events might be interconnected. These results indicate that our model may prove invaluable to uncover the molecular events leading to MYCC and TP53 alterations, which would be of broader interest considering their relevance to many human malignancies. Lastly, this mouse model might prove useful for drug screening targeting MYCC and related members of its protein interaction network.
- Subjects :
- Central Nervous System
0301 basic medicine
Pathology
Carcinogenesis
Molecular biology
Gene Expression
lcsh:Medicine
Mice, SCID
Molecular biology assays and analysis techniques
medicine.disease_cause
Nervous System
Biochemistry
Mice
Mice, Inbred NOD
Basic Helix-Loop-Helix Transcription Factors
Medicine and Health Sciences
Neuroectodermal Tumors, Primitive
Hypoxia
lcsh:Science
Cells, Cultured
Multidisciplinary
Nucleic acid analysis
Brain Neoplasms
Cell Differentiation
Animal Models
RNA analysis
Up-Regulation
medicine.anatomical_structure
Oncology
Experimental Organism Systems
RNA extraction
Anatomy
Research Article
Cell type
medicine.medical_specialty
Cns pnet
Central nervous system
Mouse Models
Biology
Research and Analysis Methods
Proto-Oncogene Proteins c-myc
03 medical and health sciences
Model Organisms
Animal model
Downregulation and upregulation
DNA-binding proteins
Genetics
medicine
Animals
Humans
Gene Regulation
Transcription factor
lcsh:R
Biology and Life Sciences
Proteins
Cell Biology
Hypoxia-Inducible Factor 1, alpha Subunit
Regulatory Proteins
Molecular biology techniques
030104 developmental biology
Cancer research
lcsh:Q
Tumor Suppressor Protein p53
Transcription Factors
Developmental Biology
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 12
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....09d2884129e6a232ab2d45c5816c5f40