Co-activator and co-repressor interplay on the human androgen receptor

Papaioannou, Maria; Reeb, Christina A.; Asim, Mohammad; Dotzlaw, Helmut; Baniahmad, Aria

doi:10.1111/j.1439-0272.2005.00690.x

Cited by 9 publications

(8 citation statements)

References 11 publications

(25 reference statements)

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“…Using CPA a co-activator/CoR competition was observed and interestingly an increasing expression of either CoR or co-activator shifts the AR towards a more repressed or activated state, respectively (Papaioannou et al, 2005).…”

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confidence: 99%

“…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).…”

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confidence: 99%

“…These results indicate that the CoR recruitment is on one hand dependent on the ARE of the target gene, suggesting a structural influence of the DNA and on the other hand on the type of ligand. A possible explanation is that a specific AR structure is imposed by both the type of ligand and the DNA sequence of a particular ARE that dictates binding specificity of CoR to the AR (Papaioannou et al, 2005).…”

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confidence: 99%

“…Hence, the AR acts as a transcription factor to transactivate or to inhibit gene expression. The transcriptional properties of the AR are partly dependent on binding of co-regulators (co-activators and co-repressors) (Brinkmann et al,1999;Burke and Baniahmad, 2000;Rosenfeld et al 2001;Feldman et al, 2001;Papaioannou et al, 2005;Baniahmad, 2005).…”

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confidence: 99%

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

Roell

Baniahmad

2011

Molecular and Cellular Endocrinology

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International audienceExtracts from the plant are widely used in the therapy of benign prostate hyperplasia (BPH) and in combinational therapy for prostate cancer, the second leading cause of cancer death and the mostly diagnosed form of cancer in men. The androgen receptor (AR) plays a crucial role in the development of the prostate as well as in prostate diseases. Even though the extracts from are considered as beneficial for prostate diseases in clinical trials, and some active compounds for treatment of BPH could be identified, compounds responsible for AR inhibition and the molecular mechanism for inhibition of prostatitis need to be identified. Recently, atraric acid and N-butylbenzene-sulfonamide were isolated from a selective dichlormethane extract of as two novel AR antagonistic compounds. The molecular mechanisms of AR inhibition were analyzed and are summarized here. Both compounds are the first known natural, complete and specific AR antagonist

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confidence: 99%

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confidence: 99%

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confidence: 99%

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confidence: 99%

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

Roell

Baniahmad

2011

Molecular and Cellular Endocrinology

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“…The transactivation function of AR can be regulated by several co-regulators (co-activators and co-repressors) [54], [55]. These proteins do not directly bind to DNA and are recruited to the promoter regions of the AR-target genes through protein-protein interactions with AR.…”

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confidence: 99%

Pterostilbene-Isothiocyanate Conjugate Suppresses Growth of Prostate Cancer Cells Irrespective of Androgen Receptor Status

et al. 2014

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Chemotherapy and anti-hormonal therapies are the most common treatments for non-organ-confined prostate cancer (PCa). However, the effectiveness of these therapies is limited, thus necessitating the development of alternative approaches. The present study focused on analyzing the role of pterostilbene (PTER)-isothiocyanate (ITC) conjugate – a novel class of hybrid compound synthesized by appending an ITC moiety on PTER backbone – in regulating the functions of androgen receptor (AR), thereby causing apoptosis of PCa cells. The conjugate molecule caused 50% growth inhibition (IC50) at 40±1.12 and 45±1.50 μM in AR positive (LNCaP) and negative (PC-3) cells, respectively. The reduced proliferation of PC-3 as well as LNCaP cells by conjugate correlated with accumulation of cells in G2/M phase and induction of caspase dependent apoptosis. Both PI3K/Akt and MAPK/ERK pathways played an important and differential role in conjugate-induced apoptosis of these PCa cells. While the inhibitor of Akt (A6730) or Akt-specific small interference RNA (siRNA) greatly sensitized PC-3 cells to conjugate-induced apoptosis, on the contrary, apoptosis was accelerated by inhibition of ERK (by PD98059 or ERK siRNA) in case of LNCaP cells, both ultimately culminating in the expression of cleaved caspase-3 protein. Moreover, anti-androgenic activity of the conjugate was mediated by decreased expression of AR and its co-activators (SRC-1, GRIP-1), thus interfering in their interactions with AR. All these data suggests that conjugate-induced inhibition of cell proliferation and induction of apoptosis are partly mediated by the down regulation of AR, Akt, and ERK signaling. These observations provide a rationale for devising novel therapeutic approaches for treating PCa by using conjugate alone or in combination with other therapeutics.

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Pleiotropic functional properties of androgen receptor mutants in prostate cancer

Bergerat¹,

Céraline

2008

Hum. Mutat.

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The androgen receptor (AR) signaling pathway plays an important role during the development of the normal prostate gland, but also during the progression of prostate cancer on androgen ablation therapy. Mutations in the AR gene emerge to keep active the AR signaling pathway and to support prostate cancer cells growth and survival despite the low levels of circulating androgens. Indeed, mutations affecting the ligand binding domain (LBD) of the AR have been shown to generate so-called "promiscuous" receptors that present widened ligand specificity and allow the stimulation of these receptors by a larger spectrum of endogenous hormones. Another class of mutations, arising in the amino-terminal domain (NTD) of the receptor, modulate AR interactions with coregulators involved in cell proliferation regulation. Besides characteristics of these well-known types of mutations, the properties of other classes of AR mutants recently described in prostate cancer are currently under investigation. Most interestingly, in addition to their potential role in the mechanisms which allow prostate cancer cells to escape androgen ablation therapy, data suggest that certain AR mutations are present early in the natural history of the disease and may play a role in many aspects of prostate cancer progression. Surprisingly, singular truncated AR devoid of their carboxy-terminal end (CTE) region seem to exert specific paracrine effects and to induce a clonal cooperation with neighboring prostate cancer cells, which may facilitate both the invasion and metastasis processes. In this article, we review the functional properties of different classes of AR mutants and their potential impact on the natural history of prostate cancer. Hum Mutat 0, 1-14, 2008. (c) 2008 Wiley-Liss, Inc.

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Co-activator and co-repressor interplay on the human androgen receptor

Cited by 9 publications

References 11 publications

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

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

Pterostilbene-Isothiocyanate Conjugate Suppresses Growth of Prostate Cancer Cells Irrespective of Androgen Receptor Status

Pleiotropic functional properties of androgen receptor mutants in prostate cancer

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