A Differential Ligand-mediated Response of Green Fluorescent Protein-tagged Androgen Receptor in Living Prostate Cancer and Non-prostate Cancer Cell Lines

Abstract

S U M M A R Y Androgen has been shown to promote the proliferation of prostate cancer through the action of the androgen receptor (AR). Mutation (T877A) of the AR gene found in an androgen-sensitive prostate cancer cell line, LNCaP, has been postulated to be involved in hypersensitivity and loss of specificity for androgen. In the present study, trafficking of AR and AR (T877A) in living prostate and non-prostate cancer cell lines under high and low concentrations of androgen and antiandrogen was investigated by tagging green fluorescent protein (GFP) to the receptors. In the presence of a high concentration of androgen, AR-GFP localized in the nucleus by forming discrete clusters in all cell lines. AR (T877A)-GFP was also translocated to the nucleus in LNCaP and COS-1 cells by the addition of a high concentration of androgen. In contrast, in the presence of a low concentration of androgen, the translocation of AR-GFP and AR (T877A)-GFP was observed in LNCaP cells, but not in COS-1 cells. Upon the addition of antiandrogen, AR-GFP was translocated to the nucleus but did not form subnuclear foci in both COS-1 and LNCaP cells, whereas AR (T877A)-GFP in both cells was translocated to the nucleus with subnuclear foci. The present study demonstrates the differential response of nuclear trafficking of AR and its mutant in prostate cancer cell lines and COS cells, and the subcellular and subnuclear compartmentalization provide important information on the sensitivity of the AR mutation. (J Histochem Cytochem 55:535-544, 2007)

Functional AR Signaling Is Evident in an In Vitro Mouse Follicle Culture Bioassay That Encompasses Most Stages of Folliculogenesis1

“…In analogy to other studies [38,[45][46][47], antagonist-induced nuclear translocation of AR immunoreactivity was seen within the first day of culture in a definite number of somatic cells. These findings demonstrate that, at least during early in vitro preantral follicular development when androgen concentrations are still low, antagonists can exert their antiandrogenic actions.…”

A multi‐parameter imaging assay identifies different stages of ligand‐induced androgen receptor activation

“…More recently, a number of fluorescent indicators have been designed for ligand-mediated responses of SRs. Some of these quantify ligand-induced activity by nuclear translocation or nuclear mobility of fluorescently labeled receptors or receptor chimeras (39)(40)(41)(42). Others make use of ligand-induced conformational changes in the SR-LBDs (43).…”

The natural compounds atraric acid and N-butylbenzene-sulfonamide as antagonists of the human androgen receptor and inhibitors of prostate cancer cell growth

“…The pure AR-antagonists such as casodex or hydroxyflutamide (OH-Fl) are non-steroidal compounds that allow the recruitment of CoR to the AR and inhibit its activity as well as the PCa proliferation (Dotzlaw et al, 2002;Song et al, 2004;Papaioannou et al, 2005;Baniahmad et al, 2005;Powell et al, 2006). Also the cellular distribution of the AR seems to be changed by these ligands (Tyagi et al, 2000;Farla et al, 2005;Marcelli et al, 2006;Nakauchi et al, 2007). The partial AR antagonist Page 4 of 28 A c c e p t e d M a n u s c r i p t…”