Androgen receptor expression of proliferating basal and luminal cells in adult murine ventral prostate

Abstract

Maintenance of the size and differentiated function of the adult prostate is dependent on testicular androgens. In this study, simultaneous androgen receptor (AR) immunohistochemistry and [3 H]thymidine labelling was used to characterise the proliferating epithelial cells of the murine ventral prostate. Proliferation in the adult prostate was more prevalent in the basal cell population with 1·8% AR-negative cells labelled with [3 H]thymidine as compared with 0·7% AR-expressing luminal cells. Three weeks following castration of mice, the atrophied prostate contained rudimentary glands composed of both luminal and basal cells with the proportion of AR-expressing basal cells reduced from 50 to 25%. Administration of testosterone enanthate to castrated mice induced a recapitulation of the prostate gland that was preceded by up-regulation of AR expression in basal cells to normal adult levels (50% AR-positive cells) by 12 h following testosterone injection. Proliferation of AR-positive luminal cells peaked at 48 h (22·8%) while proliferation of AR-negative basal cells peaked at 96 h (6·1%) following testosterone administration. These results suggest that distinct populations of luminal and basal cells are resistant to castration-induced involution of the prostate but remain responsive to direct or indirect testosterone effects and recapitulate the gland following administration of testosterone.

Basal epithelial stem cells are efficient targets for prostate cancer initiation

“…Most studies in the human report AR expression is restricted to the luminal cell layer; several studies in the mouse report widespread expression in both basal and luminal cells (16)(17)(18). qPCR and Western blot analyses demonstrate that both mRNA and protein for AR can be identified at high levels in basal/stem, luminal, and stromal cell fractions ( Fig.…”

Androgens and androgen receptor signaling in prostate tumorigenesis

“…Luminal cells express high levels of AR and respond directly to androgens by stimulating production and secretion of prostatic differentiation markers. Basal cells are usually considered to lack AR expression, but several studies have reported AR localization using immunohistochemistry in a subset of basal cells in normal human and rodent prostate specimens as well as hyperplastic human prostate samples (Bonkhoff & Remberger 1993, Mirosevich et al 1999 (Mirosevich et al 1999, Lee et al 2012. The disposition of the androgen/AR signaling axis in these cells likely influences future prostate cancer development.…”

Cancer stem cell markers in common cancers – therapeutic implications

“…The marked increase in prostate growth during puberty is largely attributable to a strong proliferation of luminal prostate cells, with the majority of basal cells remaining inactive [80]. [ 3 H] thymidine uptake studies showed that basal cells with high levels of AR are not actively involved in proliferation [84]. In addition, the recent discovery of a luminal-restricted progenitor cell population in the mammary gland supports the concept of separate basal-and luminal-derived progenitor cell populations responding independently to various growth and differentiation cues [85].…”