PLoS By Category | Recent PLoS Articles


Human a2ß1HI CD133+VE Epithelial Prostate Stem Cells Express Low Levels of Active Androgen Receptor
Published: Wednesday, November 07, 2012
Author: Stuart C. Williamson et al.

by Stuart C. Williamson, Anastasia C. Hepburn, Laura Wilson, Kelly Coffey, Claudia A. Ryan-Munden, Deepali Pal, Hing Y. Leung, Craig N. Robson, Rakesh Heer

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 (a2ß1HI CD133+VE), transiently amplifying (a2ß1HI CD133–VE) and terminally differentiated (a2ß1LOW CD133–VE) cells. AR transcript and protein expression was confirmed in a2ß1HI CD133+VE and CD133–VE progenitor cells. Flow cytometry confirmed that median (±SD) fraction of cells expressing AR were 77% (±6%) in a2ß1HI CD133+VE stem cells and 68% (±12%) in a2ß1HI CD133–VE transiently amplifying cells. However, 3-fold lower levels of total AR protein expression (peak and median immunofluorescence) were present in a2ß1HI 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.