Alien Interacts with the Human Androgen Receptor and Inhibits Prostate Cancer Cell Growth

Moehren, Udo; Papaioannou, Maria; Reeb, Christina A.; Wang, Hong; Baniahmad, Aria

doi:10.1210/me.2006-0468

Cited by 33 publications

(59 citation statements)

References 39 publications

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“…Cell culture, transient and stable transfection, growth analyses CV1 and LNCaP cells were grown as previously described (Moehren et al 2007). Transfections were performed using a modified calcium-phosphate method (Dotzlaw et al 2003).…”

Section: Methodsmentioning

confidence: 99%

“…Co-immunoprecipitation (Co-IP) was performed according to Moehren et al 2007 using LNCaP cells treated with CPA (10 K7 M) or with CPA (10 K7 M) and U0126 (10 K5 M) solved in ethanol, and harvested 30 min after application using anti-AR, PG-21, polyclonal, (Upstate, Temecula, CA, USA). Washing buffers contained CPA (10 K7 M) or CPA (10 7 M) and U0126 (10 K5 M).…”

Section: Co-immunoprecipitationmentioning

confidence: 99%

“…Chromatin immunoprecipitation (ChIP) experiment was performed essentially as described previously (Moehren et al 2007). Anti-AR antibody (PG-21; Upstate) anti-SMRT (PA1-842; Affinity BioReagents) and IgG (Santa Cruz Biotechnology).…”

Section: Chromatin Immunoprecipitation Assaymentioning

confidence: 99%

“…Isolation of mRNA and the real-time PCR was performed as described earlier (Moehren et al 2007). LNCaP cells were treated as indicated for 3 days, total cellular RNA was isolated, 1 mg RNA was reversetranscribed to cDNA and was subjected to amplification by light cycler (Roche) using specific primers and control primers against PSA and b-actin.…”

Section: Real Time Rt-pcrmentioning

confidence: 99%

“…Antihormones mediate their inhibitory function on AR in part through recruitment of corepressors to the AR, for example, the clinically used cyproterone acetate (CPA; Dotzlaw et al 2002, 2003, Moehren et al 2007. CPA acts as a partial agonist for the wild-type AR leading to AR-mediated transactivation, which is weaker compared with that induced by pure agonists.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of MAPK-signaling pathway promotes the interaction of the corepressor SMRT with the human androgen receptor and mediates repression of prostate cancer cell growth in the presence of antiandrogens

Eisold

Asim²,

Eskelinen³

et al. 2009

Journal of Molecular Endocrinology

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Prostate cancer is one of the most prominent malignancies of elderly males. The growth of normal prostate and prostate cancer (PCa) cells depend on functional androgen receptor (AR), a ligand controlled transcription factor and member of the nuclear receptor superfamily. Binding of agonistic ligand enhances the transactivation function of AR and hence promotes the growth of prostate epithelial cells. We have earlier shown that AR antagonistic ligands such as cyproterone acetate (CPA) promote the recruitment of transcriptional corepressors such as silencing mediator of retinoid and thyroid receptor (SMRT) leading to repression of AR transactivation in non-PCa cells. Unfortunately, however, in LNCaP PCa cells, CPA functions as an agonist and thereby increases AR transactivation function. Here, we show that activated MEK signaling cascade inhibits functional recruitment of corepressor SMRT to CPA-bound AR in PCa cells. Chemical blockade of MEK kinase using a specific inhibitor U0126 increases the interaction and hence repression of AR by the corepressor SMRT in LNCaP PCa cells. This inhibition also results in enhanced antagonistic behavior of CPA as assessed by reporter and cell-growth assays. Moreover, the growth of LNCaP cells stably overexpressing SMRT was more robustly inhibited in the presence of CPA and U1026. In line with this, the growth rate of LNCaP cells was decelerated in the presence of both CPA and U0126. This suggests that activated MEK signaling pathway attenuates the functional recruitment of corepressor SMRT to AR induced by antagonists and thus indicates the important role of corepressors in mediating repression of both AR transactivation and PCa cell growth by antagonists. Furthermore, these findings suggest that combining receptor antagonists with signaling inhibitors could be a beneficial approach for PCa treatment.

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Section: Methodsmentioning

confidence: 99%

Section: Co-immunoprecipitationmentioning

confidence: 99%

Section: Chromatin Immunoprecipitation Assaymentioning

confidence: 99%

Section: Real Time Rt-pcrmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Inhibition of MAPK-signaling pathway promotes the interaction of the corepressor SMRT with the human androgen receptor and mediates repression of prostate cancer cell growth in the presence of antiandrogens

Eisold

Asim²,

Eskelinen³

et al. 2009

Journal of Molecular Endocrinology

Self Cite

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Questions About Questions: Investigating How Knowledge Workers Ask and Answer Questions

Burns

Kotval

2013

Bell Labs Tech. J.

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Paradoxically, although question asking is a fundamental human activity, we frequently ask and answer questions without considering the processes we use. This paper describes two studies that ask “questions about questions,” in order to improve understanding of the often implicit processes involved in the asking and answering of questions, and to inform the design of social tools to aid knowledge workers in asking and answering questions. The first study, using a focus group methodology, led to the identification of thirteen dimensions that can be used to distinguish questions, and the development of an iterative model describing the often surprisingly complex question‐asking behavior. The second study extended the findings of the first study by analyzing usage data from an enterprise social networking application to provide insight about how questions are asked and answered using that tool. These analyses revealed significant differences in conversation patterns between question and non‐question discussions in the tool. Implications for the design of social question and answer (Q&A) applications arising from the findings of these studies are presented. © 2013 Alcatel‐Lucent.

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The effect of differentiation on 1,25 dihydroxyvitamin D‐mediated gene expression in the enterocyte‐like cell line, Caco‐2

Cui

Kłopot

Jiang

et al. 2008

Journal Cellular Physiology

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We examined 1,25 dihydroxyvitamin D (1,25(OH) 2 D 3 )-induced expression of 25-hydroxyvitamin D 3 24-hydroxylase (CYP24) and apical calcium channel (TRPV6) mRNA levels in 2, 9 and 15 day cultures Caco-2 cells that model proliferating, post-proliferative, and differentiated enterocytes. 1,25(OH) 2 D 3 -induced (10 nM, 8 h) CYP24 and TRPV6 mRNA levels were significantly greater in differentiated and post-proliferative than proliferating Caco-2 cells (> 16X and > 3X, respectively). Neither CYP24 mRNA half-life nor induction of a -298 bp rat CYP24 promoter-luciferase reporter construct (10 nM 1,25(OH) 2 D 3 , 24 h) were different between proliferating and post-proliferating Caco-2 cells. We next tested whether the blunted response of natural genes to 1,25(OH) 2 D 3 in proliferating Caco-2 cells is due to altered chromatin remodeling. VDR and coactivator protein levels do not increase with differentiation but the level of the corepressor Alien falls by 50% with differentiation. Over-expression of Alien reduced 1,25(OH) 2 D 3 -induced activity of a minimal VDRE containing promoter-luciferase construct by more than 60% in differentiated Caco-2 cells while siRNA knockdown of Alien in proliferating Caco-2 cells increased 1,25(OH) 2 D 3 -induced CYP24 mRNA level by 40%. These observations suggest that Alien is a regulator of VDR-mediated gene transcription in Caco-2 cells. In addition, we found that 1,25(OH) 2 D 3 -induced association of VDR with chromatin and with the CYP24 promoter was lower in proliferating cells. This suggests that decreased recruitment of VDR to vitamin D response elements also contributes to the blunted transcriptional responsiveness to 1,25(OH) 2 D 3 in proliferating Caco-2 cells.

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Alien Interacts with the Human Androgen Receptor and Inhibits Prostate Cancer Cell Growth

Cited by 33 publications

References 39 publications

Inhibition of MAPK-signaling pathway promotes the interaction of the corepressor SMRT with the human androgen receptor and mediates repression of prostate cancer cell growth in the presence of antiandrogens

Inhibition of MAPK-signaling pathway promotes the interaction of the corepressor SMRT with the human androgen receptor and mediates repression of prostate cancer cell growth in the presence of antiandrogens

Questions About Questions: Investigating How Knowledge Workers Ask and Answer Questions

The effect of differentiation on 1,25 dihydroxyvitamin D‐mediated gene expression in the enterocyte‐like cell line, Caco‐2

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