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Dysplasia of human prostate CD133 hi sub‐population in NOD‐SCIDS is blocked by c‐myc anti‐sense
Author(s) -
Goodyear S.M.,
Amatangelo M.D.,
Stearns M.E.
Publication year - 2009
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20918
Subject(s) - population , sense (electronics) , microbiology and biotechnology , cancer research , biology , cyclin d1 , cell , cell culture , prostate cancer , in vitro , chemistry , cancer , medicine , cell cycle , genetics , environmental health
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 ∼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. Prostate 69: 689–698, 2009. © 2009 Wiley‐Liss, Inc.