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Regulation of androgen receptor levels: Implications for prostate cancer progression and therapy
Author(s) -
Burnstein Kerry L.
Publication year - 2005
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.20460
Subject(s) - prostate cancer , androgen receptor , dihydrotestosterone , androgen , androgen deprivation therapy , cancer research , prostate , medicine , biology , endocrinology , testosterone (patch) , transcription factor , cancer , nuclear receptor , hormone , gene , genetics
Androgen deprivation has been the standard therapy for advanced and metastatic prostate cancer for over half a century, as prostate tumors are initially dependent on androgens for growth and survival. Unfortunately, in most patients undergoing androgen ablation, relapse (recurrent tumor growth) eventually occurs. The actions of the principal androgens, testosterone and dihydrotestosterone (DHT), are mediated via androgen receptors (ARs), ligand‐activated transcription factors that belong to the nuclear receptor superfamily. Because of the presence of transcriptionally active ARs in tumors from recurrent or androgen‐independent disease, there is a heightened interest in new therapeutic paradigms that target the AR and its regulatory pathways. The regulation of AR levels is highly complex with control exerted by several pathways and in a cell‐, tissue‐, and developmental‐stage specific manner. Androgens are important regulators of AR mRNA and protein through transcriptional and post‐transcriptional mechanisms. This article reviews the evidence implicating the AR in recurrent prostate cancer and discusses the multiple mechanisms that regulate AR levels in normal and neoplastic cells. The complexity of AR regulation suggests that there will be an ample array of potential new drug targets for modulating levels of this receptor, a key signaling molecule in prostate cancer. © 2005 Wiley‐Liss, Inc.