Document Details

Document Type : Article In Journal 
Document Title :
Generation of cancerous neural stem cells forming glial tumor by oncogenic stimulation
Generation of cancerous neural stem cells forming glial tumor by oncogenic stimulation
 
Document Language : English 
Abstract : Neural stem cells in the brain have been shown to be 'cells of origin' of certain brain cancers, most notably astrocytomas and medulloblastoma. In particular, in a mouse model, the targeting of genetic modifications for astrocytoma-relevant tumor suppressors to neural stem cells causes malignant astrocytoma to arise, thereby suggesting that astrocytoma is derived from neural stem cells. However, it remains to be determined whether this important finding is reproducible in humans. Herein, we generated cancerous neural stem cells by introducing a set of oncogenes to human fetal neural stem cells (hfNSCs). Serial genetic modification with v-myc for immortalization and consequent H-Ras for oncogenic stimulation with viral gene delivery proved sufficient to induce the transformation of hfNSCs. The resultant F3.Ras cells evidenced a variety of the hallmarks of brain cancer stem cells and most importantly were tumorigenic, forming brain cancers consisting of both a large number of differentiated and a very few undifferentiated populations of cells in an in vivo mouse model. On the contrary, oligodendrocytes derived from the v-myc expressing parent neural stem cells were not transformed by H-Ras, which suggests that neural stem cells may be more susceptible to cancerous transformation by a combination of oncogenes. We also determined that v-myc expressing fetal neural stem cells were defective in p53 response upon the introduction of H-Ras; this finding suggests that an insufficient p53-dependent tumor suppressive mechanism would be associated with high oncogenic susceptibility to H-Ras introduction. 
ISSN : 1550-8943 
Journal Name : Stem Cell Reviews and Reports 
Volume : 8 
Issue Number : 2 
Publishing Year : 1433 AH
2012 AD 
Article Type : Article 
Added Date : Thursday, March 10, 2016 

Researchers

Researcher Name (Arabic)Researcher Name (English)Researcher TypeDr GradeEmail
Ji-Seon LeeLee, Ji-Seon Investigator  
Hong Jun LeeLee, Hong Jun Researcher  
Bo-Hyun MoonMoon, Bo-Hyun Researcher  
Seung-Hyun SongSong, Seung-Hyun Researcher  
Mi-Ok LeeLee, Mi-Ok Researcher  
Sung Han ShimShim, Sung Han Researcher  
Hyung Seok KimKim, Hyung Seok Researcher  
Min Cheol LeeLee, Min Cheol Researcher  
Jeong Taik KwonKwon, Jeong Taik Researcher  
Albert J Fornace JrFornace Jr, Albert J Researcher  

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