Norepinephrine activates P44 and P42 MAPK in human prostate stromal and smooth muscle cells but not in epithelial cells

Abstract

These results suggest that NE may stimulate the proliferation of non-epithelial prostatic cells, which may be involved in the pathogenesis of BPH.

Coupling of α₁-Adrenoceptors to ERK1/2 in the Human Prostate

“…A considerable part of prostate tissue consists of stroma, where smooth muscle cells are a major cell type [1] . This idea of a localization of ␣ 1 -adrenergic ERK activation is supported by a previous study, where ERK1/2 expression was observed in isolated cultured human prostatic smooth muscle cells [9] . Interestingly, norepinephrine induced ERK1/2 activation in cultured smooth muscle and stromal cells, but not in cultured epithelial cells in that study [9] .…”

“…This idea of a localization of ␣ 1 -adrenergic ERK activation is supported by a previous study, where ERK1/2 expression was observed in isolated cultured human prostatic smooth muscle cells [9] . Interestingly, norepinephrine induced ERK1/2 activation in cultured smooth muscle and stromal cells, but not in cultured epithelial cells in that study [9] . However, neither the type of adrenoceptor mediating this phosphorylation nor any relevance for intact human prostate tissue were identified.…”

“…Studies using extraprostatic cell lines demonstrated that ␣ 1 -adrenoceptors may additionally couple to nonmotoric signaling pathways, which are involved in growth, proliferation and differentiation [4,5] . In vivo studies in rodents and investigations using isolated cultured cells have provided evidence that prostate ␣ 1 -adrenoceptors may show such nonmotoric coupling in addition to their role in contraction [6][7][8][9] . However, any relevance in intact human prostate tissue has not been tested to date, and any nonmotoric signaling by ␣ 1 -adrenoceptors in the prostate is insufficiently understood.…”

“…In cultured prostate stroma cells, ␣ 1 -adrenoceptor stimulation may result in proliferation [9] . Extracellular signal-regulated kinase 1/2 (ERK1/2) represents an important mediator of growth and proliferation [10] .…”

Primary cell cultures as models of prostate cancer development

“…Thebault et al (2003) showed that a 1 -adrenergic receptor-stimulated signaling in normal prostate cells is preferentially coupled to storeindependent transient receptor potential (TRP) channels, as opposed to store-operated TRP channels in the prostate cancer cell line LNCaP. It should be noted, however, that other investigators found no evidence for functional a 1 -adrenergic receptors in cultured normal prostatic epithelial cells, in line with the apparent absence of these receptors in epithelia of prostatic tissues (Kanagawa et al 2003, Marinese et al 2003. Nevertheless, these investigators suggest that isoform-specific inhibitors of TRP channels may be useful for treating prostate cancer.…”