Document Detail


Dysplasia of human prostate CD133(hi) sub-population in NOD-SCIDS is blocked by c-myc anti-sense.
MedLine Citation:
PMID:  19143028     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The CD133(hi) sub-population of prostate epithelial cells has been demonstrated to possess tumor-initiating capacity consistent with that of the cancer stem cell theory. However, the involvement of oncogenes such as c-myc has not been fully elucidated in the CD133(hi) sub-population.
METHODS: We have isolated primary prostate cell strains (IBC-10a) and immortalized them by transfection with hTERT. The in vitro and in vivo tumorigenic capacity of isolated CD133(hi) and CD133(lo) cells was evaluated with respect to c-myc expression using specific sense and anti-sense oligonucleotides.
RESULTS: Freshly immortalized cells consisted of <3.3% CD133(hi)/CD24(hi) sub-population (SP). "Prostaspheres" generated from single CD133(hi) cells in the presence of EGF consisted of approximately 10% CD133(hi) SPs in 12-21 day cultures. A single Prostasphere generated from single CD133(hi) cells (6-10 cell stage at day 6 injected i.t.) produced dysplastic lesions in NOD-SCID mice (n = 4/5). Treatment of Prostaspheres from CD133(hi) SPs in vitro with c-myc or cyclin D1 anti-sense oligonucleotides totally blocked colony forming ability and growth. Furthermore, treatment of fully formed, 6-day Prostaspheres for 48 hr with c-myc anti-sense significantly reduced c-myc expression and their ability to generate lesions in NOD-SCIDs (n = 10 Prostaspheres injected i.t./mouse).
CONCLUSIONS: These data demonstrate for the first time that a single CD133(hi) cell is competent to generate Prostaspheres in vitro and that CD133(hi) Prostaspheres require c-myc to grow and form dysplastic lesions in vivo.
Authors:
S M Goodyear; M D Amatangelo; M E Stearns
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  The Prostate     Volume:  69     ISSN:  1097-0045     ISO Abbreviation:  Prostate     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-04-20     Completed Date:  2009-05-04     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  8101368     Medline TA:  Prostate     Country:  United States    
Other Details:
Languages:  eng     Pagination:  689-98     Citation Subset:  IM    
Copyright Information:
2009 Wiley-Liss, Inc.
Affiliation:
Molecular Pathobiology Program, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD / biosynthesis*
Blotting, Western
DNA, Antisense / administration & dosage,  genetics*
Flow Cytometry
Glycoproteins / biosynthesis*
Humans
Karyotyping
Male
Mice
Mice, Inbred NOD
Mice, SCID
Middle Aged
Neoplastic Stem Cells / pathology*
Peptides
Prostatic Neoplasms / genetics,  immunology,  pathology*
Proto-Oncogene Proteins c-myc / biosynthesis,  genetics*
Telomerase / genetics
Transfection
Grant Support
ID/Acronym/Agency:
NCI 232216//PHS HHS; R01 CA076639-11/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/AC133 antigen; 0/Antigens, CD; 0/DNA, Antisense; 0/Glycoproteins; 0/MYC protein, human; 0/Peptides; 0/Proto-Oncogene Proteins c-myc; EC 2.7.7.49/TERT protein, human; EC 2.7.7.49/Telomerase
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