Suppressor role of AR in prostate basal cells

Normal adult prostatic epithelium includes three types of cells: neuroendocrine cells, luminal epithelial cells, and basal epithelial cells that are aligned along the basement membrane. Cells in the luminal layer express androgen receptor (AR), prostate-specific antigen (PSA), cytokeratin-8 (CK8), and CK18. In contrast, cells of the basal layer express CK5 and CK14, and AR expression is either undetectable or at a very low level. Under normal conditions, adult prostate epithelial cells remain in homeostasis with infrequent turnover. However, the homeostasis is broken upon androgen depletion. When an adult male is castrated, the serum testosterone level decreases rapidly and the prostate regresses with the majority of luminal epithelial cells dying through apoptosis, whereas the majority of basal epithelial cells remain alive.

Earlier in vitro studies using different prostate epithelial cell lines led to different conclusions that androgen might be able to either stimulate or suppress prostate epithelial cell proliferation. These contrasting results suggest that response to androgen deprivation treatment is different in normal luminal epithelial cells vs basal epithelial cells. Using established mouse and human basal epithelial/progenitor cells as well as an in vivo basal-ARKO (Cyp19a1) mouse model, Lee et al. report that ARs may play a negative role to suppress proliferation of basal epithelial/progenitor cells, yet AR expression also plays essential roles to drive these cells into a more differentiated state.

These results may explain why differential AR expression in different cell types within normal prostate is needed and suggest that ARs in prostate basal epithelial cells, although expressed at a very low level, are necessary to maintain the balance between progenitor cells and differentiated luminal epithelial cells. Lee et al. (2012) Journal of Endocrinology 213 173-182.

Read the full article at DOI: 10.1530/JOE-11-0474