Trafficking of the androgen receptor in living cells with fused green fluorescent protein–androgen receptor

Georget, Virginie; Lobaccaro, Jean‐Marc; Térouanne, Béatrice; Mangeat, Paul; Nicolas, Jean‐Claude; Sultan, Charles

doi:10.1016/s0303-7207(97)04034-3

Cited by 171 publications

(115 citation statements)

References 24 publications

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“…The lack of AR immunoreaction for spermatogonial subtypes is also consistent with previous reports (Bremner et al, 1994;Vornberger et al, 1994;Matsumiya et al, 1999). AR functions as a ligand-dependent transcription factor, since ligand binding is a prerequisite for its transport to the nucleus where it accesses and regulates an array of androgen-responsive genes (Georget et al, 1997;Wang et al, 2009). The regulation of AR functionality is far from being understood but their cytoplasmic localization has been usually interpreted as an inactivated state (Tyagi et al, 2000).…”

Section: Discussionsupporting

confidence: 91%

Neonatal Gonocyte Differentiation in Mongolian GerbilMeriones unguiculatusInvolves Asynchronous Maturation of Seminiferous Cords and Rapid Formation of Transitional Cell Stage

Pinto

Botta

Taboga

et al. 2010

The Anatomical Record

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This study describes the neonatal differentiation of the Mongolian gerbil gonocytes, focusing on the relationship between its relocation to the basement membrane, apoptosis and postrelocation changes and also the distribution of androgen receptors (AR). Testes of gerbils from 1 to 35 days of age (d) were examined by high resolution light microscopy and immunocytochemistry for proteins PCNA, VASA, and AR as well as by the TUNEL method. Gonocytes were quantified according to degree of relocation into nonrelocated, relocating and relocated. Most of them were found in the center of seminiferous cords at 1 d but a small number of relocating and relocated gonocytes were already visible in the first postnatal day. After relocation, gonocytes change phenotypically to a transitional stage designated herein prospermatogonia. Both gonocyte relocation and transformation into spermatogonial lineage occur asynchronously in the seminiferous cords, mainly after 7 d. Gonocyte proliferation began before but peak after their relocation to basement membrane at the prospermatogonia stage. Higher levels of gonocyte apoptosis were found at 7 d and 21 d. From this time onward gonocytes were not found. Gonocytes and prospermatogonia showed high amounts of AR in their cytoplasm contrary to spermatogonial subtypes, indicating a possible AR inactivation in these cells. In conclusion, the process of gonocyte relocation in the gerbil extends until the second postnatal week, leads to their rapid differentiation into prospermatogonia and occurs simultaneously with the loss of androgen sensitivity. Differently from other laboratory rodents, the events regarding gonocyte maturation in the gerbil last longer and occur asynchronously in seminiferous cords. Anat Rec,

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Section: Discussionsupporting

confidence: 91%

Neonatal Gonocyte Differentiation in Mongolian GerbilMeriones unguiculatusInvolves Asynchronous Maturation of Seminiferous Cords and Rapid Formation of Transitional Cell Stage

Pinto

Botta

Taboga

et al. 2010

The Anatomical Record

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“…We show that all antiandrogens tested retain AR in the cytoplasm of PC3wtAR cells to varying degrees. The retention appears to be greater than that in transiently transfected cells (6,7,9). We propose that this partial cytoplasmic retention may be a more accurate reflection of the movement of endogenous AR and that complete nuclear translocation in the presence of antiandrogens in transfected cells could be an artifact of transient AR overexpression.…”

Section: Discussionmentioning

confidence: 73%

“…Conversely, unliganded glucocorticoid receptor resides entirely in the cytoplasm (4). There is controversy concerning the localization of unliganded AR: different groups have reported predominantly cytoplasmic or nuclear localization (5)(6)(7)(8)(9). The current consensus is that unliganded AR resides largely in the cytoplasm, complexed with heat shock proteins (10).…”

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

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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.

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“…1 The abbreviations used are: AR, androgen receptor; GST, glutathione transferase; DHT, dihydrotesteosterone; ARE, androgen-responsive element; DBD, DNA-binding domain; LBD, ligand-binding domain; HA, hemagglutinin antigen; CMV, cytomegalovirus; PAGE, polyacrylamide gel electrophoresis; Mes, 4-morpholineethanesulfonic acid.…”

mentioning

confidence: 99%

Caveolin-1 Interacts with Androgen Receptor

Lu¹,

Schneider

Zheng³

et al. 2001

Journal of Biological Chemistry

213

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Androgen receptor (AR) belongs to the steroid hormone nuclear receptor superfamily. It functions as an androgen-dependent transcriptional factor that regulates genes for cell proliferation and differentiation. Caveolin is a principal component of caveolae membranes serving as a scaffold protein of many signal transduction pathways. Recent results correlate caveolin-1 expression with androgen sensitivity in murine prostate cancer. Furthermore, immunohistochemical staining of patient specimens suggests that caveolin expression may be an independent predictor of progression of prostate cancer. In this study, we investigate the potential interactions between AR signaling and caveolin-1 and demonstrate that overexpression of caveolin-1 potentiates ligand-dependent AR activation. Conversely, down-regulation of caveolin-1 expression by a caveolin-1 antisense expression construct can downregulate ligand-dependent AR activation. Association between these two molecules is also demonstrated by co-localization of AR with caveolin-rich, low-density membrane fractions isolated by an equilibrium sucrose gradient centrifugation method. Co-immunoprecipitation and glutathione S-transferase fusion protein pulldown experiments demonstrate that interaction between AR and caveolin-1 is an androgen-dependent process, offering further evidence for a physiological role of this interaction. Using a mammalian two-hybrid assay system, we determine that the NH 2 terminus region of caveolin-1 is responsible for the interaction with both the NH 2 -terminal domain and the ligand-binding domain of AR.

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Trafficking of the androgen receptor in living cells with fused green fluorescent protein–androgen receptor

Cited by 171 publications

References 24 publications

Neonatal Gonocyte Differentiation in Mongolian GerbilMeriones unguiculatusInvolves Asynchronous Maturation of Seminiferous Cords and Rapid Formation of Transitional Cell Stage

Neonatal Gonocyte Differentiation in Mongolian GerbilMeriones unguiculatusInvolves Asynchronous Maturation of Seminiferous Cords and Rapid Formation of Transitional Cell Stage

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

Caveolin-1 Interacts with Androgen Receptor

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