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Updated: Jun 26, 2026
Murine Prostate Micro-dissection and Surgical Castration
Published on: May 11, 2016
Dysplasia of human prostate CD133(hi) sub-population in NOD-SCIDS is blocked by c-myc anti-sense
S M Goodyear1, M D Amatangelo, M E Stearns
1Molecular Pathobiology Program, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.
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.
Insights
Cancer stem cells, identified as CD133(hi) prostate cells, require the oncogene c-myc to form tumors. Inhibiting c-myc in these CD133(hi) cells blocks their growth and tumor-forming ability.
Area of Science:
- Prostate cancer research
- Cancer stem cell biology
- Oncogene function
Background:
- The CD133(hi) subpopulation of prostate cells exhibits cancer stem cell properties.
- The role of oncogenes like c-myc in CD133(hi) cells is not fully understood.
Purpose of the Study:
- To investigate the role of c-myc in the tumor-initiating capacity of CD133(hi) prostate cells.
- To evaluate the effect of c-myc inhibition on the growth and tumorigenesis of CD133(hi) cells.
Main Methods:
- Isolation and immortalization of primary prostate cells (IBC-10a).
- Generation of prostaspheres from CD133(hi) and CD133(lo) cells.
- In vitro and in vivo evaluation of tumorigenic capacity using c-myc antisense oligonucleotides.
Main Results:
- Single CD133(hi) cells formed prostaspheres capable of generating dysplastic lesions in vivo.
- Inhibition of c-myc or cyclin D1 using antisense oligonucleotides blocked prostasphere colony formation.
- c-myc antisense treatment reduced c-myc expression and lesion formation in vivo.
Conclusions:
- A single CD133(hi) cell can initiate prostasphere formation and tumor development.
- CD133(hi) prostaspheres depend on c-myc for growth and in vivo tumorigenesis.
