title: Growth kinetics of CD133-positive prostate cancer cells.
abstract: BACKGROUND
  In the adult human prostate CD133 expression is thought to mark rare prostate epithelial stem cells and malignant tumor stem/initiating cells. Such putative stem cell populations are thought to proliferate slowly, but possess unlimited proliferative potential. Based on this, we hypothesized that CD133(pos) prostate cancer cells proliferate slower than CD133(neg) cells.
  
  
  METHODS
  Human prostate cancer cell lines were analyzed for CD133 expression and DNA content using flow cytometry. Rates of cell division and DNA synthesis were determined using CFSE cell tracing and BrdU uptake, respectively. Changes in cell cycle distribution and the percentage of CD133(pos) cells were assayed under conditions of different cell density and AR-pathway modulation. Lastly, we over-expressed lentiviral CD133 to measure whether CD133 regulates the cell cycle.
  
  
  RESULTS
  The cell cycle distribution differs between CD133(pos) and CD133(neg) cells in all three human prostate cancer cell lines studied. CD133(pos) cells have a greater proportion of cells in G2 and proliferate faster than CD133(neg) cells. High cell density increases the percentage of CD133(pos) cells without changing CD133(pos) cell cycle progression. Treatment with the AR agonist R1881, or the anti-androgen MDV3100, significantly changed the percentage and proliferation of CD133(pos) cells. Finally, ectopic over-expression of CD133 had no effect on cell cycle progression.
  
  
  CONCLUSIONS
  Contrary to our hypothesis, we demonstrate that CD133(pos) cells proliferate faster than CD133(neg) cells. This association of CD133 expression with increased cell proliferation is not directly mediated by CD133, suggesting that surface CD133 is a downstream target gene of an undefined pathway controlling cell proliferation.
authors.affiliation: Committee on Immunology, The University of Chicago, Chicago, IL, USA.
authors.forename: Edwin E
authors.initials: EE
authors.lastname: Reyes
authors.forename: Stefan K
authors.initials: SK
authors.lastname: Kunovac
authors.forename: Ryan
authors.initials: R
authors.lastname: Duggan
authors.forename: Steven
authors.initials: S
authors.lastname: Kregel
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Vander Griend
mesh_terms: D000071916:AC133 Antigen; D000726:Androgen Antagonists / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008297:Male; D010455:Peptides / Q000378:metabolism*; D011467:Prostate / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000071916:AC133 Antigen; D000726:Androgen Antagonists; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides