Interaction of antiandrogen-androgen receptor complexes with DNA and transcription activation

Warriar, Nalini; Pagé, Nathalie; Koutsilieris, Michael; Govindan, Manjapra V.

doi:10.1016/0960-0760(93)90311-j

Cited by 21 publications

(6 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cyproterone acetate induced a very modest activation (ϳ2-fold) from both pMMTV-Luc and pARE 2 -DS-Luc in E19 cells (Figs. 7A and 7B), consistent with the notion of a partial agonistic activity of this compound (38), while flutamide failed to signif-…”

Section: Transcriptional Activity Of F:ar In E19 Cellssupporting

confidence: 85%

Generation of a Mammalian Cell Line Stably Expressing a Tetracycline-Regulated Epitope-Tagged Human Androgen Receptor: Implications for Steroid Hormone Receptor Research

Wang

Fondell

2001

Analytical Biochemistry

View full text Add to dashboard Cite

Section: Transcriptional Activity Of F:ar In E19 Cellssupporting

confidence: 85%

Generation of a Mammalian Cell Line Stably Expressing a Tetracycline-Regulated Epitope-Tagged Human Androgen Receptor: Implications for Steroid Hormone Receptor Research

Wang

Fondell

2001

Analytical Biochemistry

View full text Add to dashboard Cite

“…However, coincubation of DHT with OHF abrogated the DHT inhibition (OHF+DHT vs DHT, P<0·001). Although OHF alone slightly reduced MTT activity due to modest agonist effects of high concentration of OHF in the absence of androgen (Warriar et al 1993), this inhibition did not reach significance compared with control. OHF alone was significantly different from DHT+OHF (P,0·01).…”

Section: Androgen Inhibition During Osteoblast Proliferationmentioning

confidence: 91%

“…Cells were generally plated in control or hormone-containing media, and grown for 5 days before isolation. DHT treatment at 10 8 M was at the end of growth, either continuous (5 days) or for the last 48 or 72 h. The non-steroidal aromatic anti-androgen OHF has been shown to antagonize androgen regulation of gene expression, but has a relatively low affinity for the AR (Warriar et al 1993). Thus, a several hundred-fold to 1000-fold molar excess of OHF over DHT is required for effective blockage of the DHT effect (Kemppainen et al 1992).…”

Section: Mtt Assay For Cell Viabilitymentioning

confidence: 99%

Androgen inhibition of MAP kinase pathway and Elk-1 activation in proliferating osteoblasts

Wiren¹,

Toombs²,

Xw³

2004

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

Non-aromatizable androgens have significant beneficial effects on skeletal homeostasis independently of conversion to estradiol, but the effects of androgens on bone cell metabolism and cell proliferation are still poorly understood. Using an osteoblastic model with enhanced androgen responsiveness, MC3T3-E1 cells stably transfected with androgen receptor (AR) under the control of the type I collagen promoter (colAR-MC3T3), the effects of androgens on mitogenic signaling were characterized. Cultures were treated with the non-aromatizable androgen 5 -dihydrotestosterone (DHT) and the effects on osteoblast viability were determined as measured by an MTT assay. A complex response was observed in that continuous short-term DHT treatment enhanced osteoblast viability, but with longer-term DHT treatment inhibition was observed. The inhibition by DHT was prevented by the specific AR antagonist hydroxyflutamide, and was also observed in primary cultures of normal rat calvarial osteoblasts. In order to identify potential mediators of this effect, mitogenic pathway-specific cDNA microarrays were interrogated. Reduced hybridization of several genes important in MAP kinase-mediated signaling was observed, with the most dramatic effect on Elk-1 expression. Analysis of phosphorylation cascades demonstrated that DHT treatment inhibited phosphoERK1/2 levels, MAP kinase activation of Elk-1, Elk-1 protein and phosphoElk-1 levels, and downstream AP-1/luciferase reporter activity. Together, these data provide the first evidence that androgen inhibition of the MAP kinase signaling pathway is a potential mediator of osteoblast growth, and are consistent with the hypothesis that the MAP cascade may be a specific downstream target of DHT.

show abstract

“…Although these factors may contribute to the overall effect of the drugs, they do not account for all their actions. In some systems antiandrogens have been shown to promote AR nuclear import and even DNA binding while still inhibiting androgen-responsive gene transcription (5,6,11,12). Using reporter assays, several groups have shown partial AR activation in the presence of the therapeutic antiandrogens hydroxyflutamide (OHF) and cyproterone acetate (CPA), thus these are termed partial antagonists.…”

Section: Introductionmentioning

confidence: 99%

Androgen Receptor Is Targeted to Distinct Subcellular Compartments in Response to Different Therapeutic Antiandrogens

Whitaker

Hanrahan²,

Totty³

et al. 2004

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Antiandrogens are routinely used in the treatment of prostate cancer. Although they are known to prevent activation of the androgen receptor (AR), little is known about the mechanisms involved. This report represents the first study of the localization of wild-type AR following expression at physiologic relevant levels in prostate cells and treatment with androgen and antiandrogens.Experimental Design: We have characterized a cellular model for prostate cancer using in situ cellular fractionation, proteomics, and confocal microscopy and investigated the effect of antiandrogens in clinical use on the subcellular localization of the AR.Results: Different antiandrogens have diverse effects on the subcellular localization of the AR. Treatment with androgen results in translocation from the cytoplasm to the nucleoplasm, whereas the antiandrogens hydroxyflutamide and bicalutamide lead to reversible association with the nuclear matrix. In contrast, treatment with the antiandrogen cyproterone acetate results in AR association with cytoplasmic membranes and irreversible retention within the cytoplasm. In addition, we demonstrate that AR translocation requires ATP and the cytoskeleton, regardless of ligand.Conclusions: These results reveal that not all antiandrogens work via the same mechanism and suggest that an informed sequential treatment regime may benefit prostate cancer patients. The observed subnuclear and subcytoplasmic associations of the AR suggest new areas of study to investigate the role of the AR in the response and resistance of prostate cancer to antiandrogen therapy.

show abstract

Interaction of antiandrogen-androgen receptor complexes with DNA and transcription activation

Cited by 21 publications

References 39 publications

Generation of a Mammalian Cell Line Stably Expressing a Tetracycline-Regulated Epitope-Tagged Human Androgen Receptor: Implications for Steroid Hormone Receptor Research

Generation of a Mammalian Cell Line Stably Expressing a Tetracycline-Regulated Epitope-Tagged Human Androgen Receptor: Implications for Steroid Hormone Receptor Research

Androgen inhibition of MAP kinase pathway and Elk-1 activation in proliferating osteoblasts

Androgen Receptor Is Targeted to Distinct Subcellular Compartments in Response to Different Therapeutic Antiandrogens

Contact Info

Product

Resources

About