Androgen receptor isoforms expression in benign prostatic hyperplasia and primary prostate cancer

• DOI: 10.1371/journal.pone.0200613
• Publication Date: 2018-07-20T17:28:40Z
• Authors: Ana Caroline Hill...; Lolita Schneider ...; Brasil Silva Neto; Gisele Branchini; Ilma Simoni Brum
• Keywords: Male; Science; Prostatic Hyperplasia; 03 medical and health sciences; 0302 clinical medicine; Humans; Protein Isoforms; RNA, Messenger; Aged; Cell Nucleus; Prostatectomy; Gene Expression Profiling; Q; R; Prostate; Prostatic Neoplasms; Epithelial Cells; Middle Aged; Prostate-Specific Antigen; 3. Good health; Receptors, Androgen; Medicine; Kallikreins; Neoplasm Recurrence, Local; Research Article

The role of molecular changes in the androgen receptor (AR) as AR variants (AR-Vs) is not clear in the pathophysiology of benign prostatic hyperplasia (BPH) and hormone-naïve PCa. The aim of the current work was to identify the presence of AR isoforms in benign tissue and primary PCa, and to evaluate the possible association with tumor aggressiveness and biochemical recurrence in primary PCa. The mRNA levels of full length AR (AR-FL) and AR-Vs (AR-V1, AR-V4 and AR-V7) were measured using RT-qPCR. The protein expression of AR-FL (AR-CTD and AR-NTD) and AR-V7 were evaluated by the H-Score in immunohistochemistry (IHC). All investigated mRNA targets were expressed both in BPH and PCa. AR-FL mRNA levels were similar in both groups. AR-V4 mRNA expression showed higher levels in BPH, and AR-V1 and AR-V7 mRNA expression were higher in PCa. The AR-V7 protein showed a similar H-Score in both groups, while AR-CTD and AR-NTD were higher in nuclei of epithelial cells from BPH. These results support the assumption that these constitutively active isoforms of AR are involved in the pathophysiology of primary PCa and BPH. The role of AR-Vs and their possible modulation by steroid tissue levels in distinct types of prostate tumors needs to be elucidated to help guide the best clinical management of these diseases.