Human α2β1HI CD133+VE Epithelial Prostate Stem Cells Express Low Levels of Active Androgen Receptor

Tang, Yao Liang, Williamson, Stuart, Hepburn, Anastasia, Wilson, Laura, Coffey, Kelly, Ryan-Munden, Claudia, Pal, Deepali, Leung, Hing, Robson, Craig and Heer, Rakesh (2012) Human α2β1HI CD133+VE Epithelial Prostate Stem Cells Express Low Levels of Active Androgen Receptor. PLoS ONE, 7 (11). e48944. ISSN 1932-6203

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Abstract

Stem cells are thought to be the cell of origin in malignant transformation in many tissues, but their role in human prostate carcinogenesis continues to be debated. One of the conflicts with this model is that cancer stem cells have been described to lack androgen receptor (AR) expression, which is of established importance in prostate cancer initiation and progression. We re-examined the expression patterns of AR within adult prostate epithelial differentiation using an optimised sensitive and specific approach examining transcript, protein and AR regulated gene expression. Highly enriched populations were isolated consisting of stem (α2β1HI CD133+VE), transiently amplifying (α2β1HI CD133–VE) and terminally differentiated (α2β1LOW CD133–VE) cells. AR transcript and protein expression was confirmed in α2β1HI CD133+VE and CD133–VE progenitor cells. Flow cytometry confirmed that median (±SD) fraction of cells expressing AR were 77% (±6%) in α2β1HI CD133+VE stem cells and 68% (±12%) in α2β1HI CD133–VE transiently amplifying cells. However, 3-fold lower levels of total AR protein expression (peak and median immunofluorescence) were present in α2β1HI CD133+VE stem cells compared with differentiated cells. This finding was confirmed with dual immunostaining of prostate sections for AR and CD133, which again demonstrated low levels of AR within basal CD133+VE cells. Activity of the AR was confirmed in prostate progenitor cells by the expression of low levels of the AR regulated genes PSA, KLK2 and TMPRSS2. The confirmation of AR expression in prostate progenitor cells allows integration of the cancer stem cell theory with the established models of prostate cancer initiation based on a functional AR. Further study of specific AR functions in prostate stem and differentiated cells may highlight novel mechanisms of prostate homeostasis and insights into tumourigenesis.

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