PMID- 17615543
OWN - NLM
STAT- MEDLINE
DCOM- 20070807
LR  - 20211203
IS  - 1090-0535 (Electronic)
IS  - 1090-0535 (Linking)
VI  - 13
DP  - 2007 Jun 8
TI  - Human embryonic and neuronal stem cell markers in retinoblastoma.
PG  - 823-32
AB  - PURPOSE: Retinoblastoma (RB) is the most common intraocular tumor of early 
      childhood. The early onset of RB, coupled with our previous findings of cancer 
      stem cell characteristics in RB, led us to hypothesize that subpopulations of RB 
      tumors harbor markers and behaviors characteristic of embryonic and neuronal 
      origin. METHODS: Our RB sources included: human pathological tissues, and the 
      human RB cell lines Y79 and WERI-RB27. Microarray screening, single and 
      dual-label immunocytochemistry and RT-PCR were performed to detect embryonic and 
      neuronal stem cell markers, such as Oct3/4, Nanog, CD133, and Musashi-1. To test 
      for functional evidence of stem cell behavior, we examined RB cells for their 
      ability to form neurospheres and retain BrdU label as indicators of self-renewal 
      and slow cell cycling, respectively. RESULTS: Microarray comparisons of human RB 
      tumors with normal retinal tissue detected upregulation of a number of genes 
      involved in embryonic development that were also present in Y79 cells, including 
      Oct3/4, Nanog, Musashi-1 and Musashi-2, prominin-1 (CD133), Jagged-2, Reelin, 
      Thy-1, nestin, Meis-1,NCAM, Patched, and Notch4. Expression of Musashi-1, Oct3/4 
      and Nanog was confirmed by immunostaining and RT-PCR analyses of RB tumors and RB 
      cell lines. CD133 expression was confirmed by PCR analysis. Y79 and WERI-RB27 
      contained populations of Hoechst-dim/ABCG2-positive cells that co-localized with 
      embryonic stem cell markers Oct3/4-ABCG2 and Nanog-ABCG2. Subpopulations of Y79 
      and WERI-RB27 cells were label-retaining (as seen by BrdU incorporation) and were 
      able to generate neurospheres, both hallmarks of a stem cell phenotype. 
      CONCLUSIONS: Small subpopulation(s) of RB cells express human embryonic and 
      neuronal stem cell markers. There are also subpopulations that demonstrate 
      functional behavior (label retention and self-renewal) consistent with cancer 
      stem cells. These findings support the hypothesis that RB is a heterogeneous 
      tumor comprised of subpopulation(s) with stem cell-like properties.
FAU - Seigel, Gail M
AU  - Seigel GM
AD  - Ross Eye Institute, University of Buffalo, Buffalo, NY 14214, USA. 
      gseigel@frontiernet.net
FAU - Hackam, Abigail S
AU  - Hackam AS
FAU - Ganguly, Arupa
AU  - Ganguly A
FAU - Mandell, Lorrie M
AU  - Mandell LM
FAU - Gonzalez-Fernandez, Federico
AU  - Gonzalez-Fernandez F
LA  - eng
GR  - P30 EY014801/EY/NEI NIH HHS/United States
GR  - R01 EY009412/EY/NEI NIH HHS/United States
GR  - R01EY009412/EY/NEI NIH HHS/United States
GR  - 5R24EY016662/EY/NEI NIH HHS/United States
GR  - R24 EY016662/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070608
PL  - United States
TA  - Mol Vis
JT  - Molecular vision
JID - 9605351
RN  - 0 (ABCG2 protein, human)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 2)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Biomarkers)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (MSI1 protein, human)
RN  - 0 (NANOG protein, human)
RN  - 0 (Nanog Homeobox Protein)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Octamer Transcription Factor-3)
RN  - 0 (POU5F1 protein, human)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Reelin Protein)
RN  - EC 3.4.21.- (RELN protein, human)
RN  - EC 3.4.21.- (Reln protein, mouse)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 2
MH  - ATP-Binding Cassette Transporters/metabolism
MH  - Animals
MH  - Biomarkers/metabolism
MH  - Cell Line
MH  - DNA-Binding Proteins/genetics/immunology/metabolism
MH  - Embryonic Stem Cells/*metabolism
MH  - Genes, Neoplasm
MH  - Homeodomain Proteins/genetics/immunology/metabolism
MH  - Humans
MH  - Mice
MH  - Nanog Homeobox Protein
MH  - Neoplasm Proteins/metabolism
MH  - Nerve Tissue Proteins/genetics/metabolism
MH  - Neurons/*metabolism
MH  - Octamer Transcription Factor-3/genetics/immunology/metabolism
MH  - Protein Transport
MH  - RNA-Binding Proteins/genetics/metabolism
MH  - Reelin Protein
MH  - Retina/metabolism/pathology
MH  - Retinoblastoma/immunology/*pathology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Up-Regulation/genetics
PMC - PMC2768758
EDAT- 2007/07/07 09:00
MHDA- 2007/08/08 09:00
PMCR- 2007/01/01
CRDT- 2007/07/07 09:00
PHST- 2007/07/07 09:00 [pubmed]
PHST- 2007/08/08 09:00 [medline]
PHST- 2007/07/07 09:00 [entrez]
PHST- 2007/01/01 00:00 [pmc-release]
AID - v13/a90 [pii]
AID - a90 [pii]
PST - epublish
SO  - Mol Vis. 2007 Jun 8;13:823-32.