Growth kinetics of CD133‐positive prostate cancer cells. Issue 7 (8th November 2012)

• Record Type: Journal Article
• Authors: Reyes, Edwin E.; Kunovac, Stefan K.; Duggan, Ryan; Kregel, Steven; Griend, Donald J. Vander
• Is Part Of: Prostate. Volume 73:Issue 7(2013)
• Page Start: 724
• Page End: 733
• Publication Date: 2012-11-08
• Subjects: CD133 -- androgen receptor -- prostate cancer -- cancer stem cell -- castration‐resistance -- cell cycle -- G2‐phase; Prostate -- Diseases -- Periodicals; 616
• DOI: 10.1002/pros.22616
• Languages: English
• ISSNs: 0270-4137

Abstract

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. Prostate 73: 724–733, 2013. © 2012 Wiley Periodicals, Inc.