Membrane testosterone binding sites in prostate carcinoma as a potential new marker and therapeutic target: Study in paraffin tissue sections

The aim of this study was to investigate whether membrane androgen receptors are differentially expressed in prostate carcinomas, and their relationship to the tumor grade. We examined the expression of membrane androgen receptors in archival material of 109 prostate carcinomas and 103 benign prostate hyperplasias, using fluorescein-labeled BSA-coupled testosterone.We report that membrane androgen receptors are preferentially expressed in prostate carcinomas, and they correlate to their grade using the Gleason's microscopic grading score system.We conclude that membrane androgen receptors may represent an index of tumor aggressiveness and possibly specific targets for new therapeutic regimens.The biological activity of androgen occurs predominantly through binding to an intracellular androgen receptor (iAR) protein, a member of the nuclear receptor superfamily, functioning as a ligand-activated transcription factor [1]. However, in recent years, a number of reports indicate additional rapid androgen actions, including the rapid activation of kinase-signaling cascades, modification of actin cytoskeleton and modulation of intracellular calcium levels [see [2,3], for reviews]. These actions are considered to be non-genomic in nature because they occur in cells lacking functional iARs in the presence of inhibitors of transcription and translation, or are observed too rapidly to involve changes in gene transcription [4].We have previously identified membrane androgen receptor (mAR) sites in prostate and breast cancer cell lines [5-7]. In a preliminary work performed on freshly prepared epithelial cells from prostate carcinoma, non-cancerous peritumoral tissue, and benign prostate hyperplasia (BPH), we have shown that mARs are expressed preferentially on carcinoma cells [8]. Activation of mARs induces actin cytoskeleton polymerization and redistribution [5,9], secretion of Prostate Specific Antigen (PSA) and apoptosis [6,7]. Membrane androgen receptor sites were responsib