PMID- 17332509
OWN - NLM
STAT- MEDLINE
DCOM- 20070816
LR  - 20171116
IS  - 1066-5099 (Print)
IS  - 1066-5099 (Linking)
VI  - 25
IP  - 6
DP  - 2007 Jun
TI  - Spontaneous transformation of human adult nontumorigenic stem cells to cancer 
      stem cells is driven by genomic instability in a human model of glioblastoma.
PG  - 1478-89
AB  - The presence of a CD133+/nestin+ population in brain tumors suggests that a 
      normal neural stem cell may be the cell of origin for gliomas. We have identified 
      human CD133-positive NSCs from adult glioma tissue and established them as 
      long-term in vitro cultures human neuroglial culture (HNGC)-1. Replicative 
      senescence in HNGC-1 led to a high level of genomic instability and emergence of 
      a spontaneously immortalized clone that developed into cell line HNGC-2 with 
      features of cancer stem cells (CSCs), which include the ability for self-renewal 
      and the capacity to form CD133-positive neurospheres and develop intracranial 
      tumors. The data from our study specify an important role of genomic instability 
      in initiation of transformed state as well as its progression into highly 
      tumorigenic CSCs. The activated forms of Notch and Hes isoforms were expressed in 
      both non-neoplastic neural stem cells and brain tumor stem cells derived from it. 
      Importantly, a significant overexpression of these molecules was found in the 
      brain tumor stem cells. These findings suggest that this model comprised of 
      HNGC-1 and HNGC-2 cells would be a useful system for studying pathways involved 
      in self-renewal of stem cells and their transformation to cancer stem cells. 
      Disclosure of potential conflicts of interest is found at the end of this 
      article.
FAU - Shiras, Anjali
AU  - Shiras A
AD  - National Centre for Cell Science (NCCS), NCCS Complex, University of Pune Campus, 
      Ganeshkhind, Pune 411007, Maharashtra, India. anjalishiras@nccs.res.in
FAU - Chettiar, Sivarajan T
AU  - Chettiar ST
FAU - Shepal, Varsha
AU  - Shepal V
FAU - Rajendran, Ganeshkumar
AU  - Rajendran G
FAU - Prasad, G Rajendra
AU  - Prasad GR
FAU - Shastry, Padma
AU  - Shastry P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070301
PL  - England
TA  - Stem Cells
JT  - Stem cells (Dayton, Ohio)
JID - 9304532
RN  - EC 2.7.7.49 (Telomerase)
SB  - IM
MH  - Adult Stem Cells/*pathology
MH  - Animals
MH  - Brain Neoplasms/genetics/*pathology
MH  - Cell Proliferation
MH  - Cell Transformation, Neoplastic/*genetics
MH  - Cellular Senescence/genetics
MH  - Genomic Instability/*physiology
MH  - Glioblastoma/genetics/*pathology
MH  - Humans
MH  - Mice
MH  - Mice, Nude
MH  - *Models, Biological
MH  - Neoplasm Invasiveness/genetics/pathology
MH  - Neoplastic Stem Cells/enzymology/metabolism/*pathology
MH  - Telomerase/metabolism
MH  - Tumor Cells, Cultured
EDAT- 2007/03/03 09:00
MHDA- 2007/08/19 09:00
CRDT- 2007/03/03 09:00
PHST- 2007/03/03 09:00 [pubmed]
PHST- 2007/08/19 09:00 [medline]
PHST- 2007/03/03 09:00 [entrez]
AID - 2006-0585 [pii]
AID - 10.1634/stemcells.2006-0585 [doi]
PST - ppublish
SO  - Stem Cells. 2007 Jun;25(6):1478-89. doi: 10.1634/stemcells.2006-0585. Epub 2007 
      Mar 1.