scholarly journals CR6-Interacting Factor 1 Represses the Transactivation of Androgen Receptor by Direct Interaction

2008 ◽  
Vol 22 (1) ◽  
pp. 33-46 ◽  
Author(s):  
Ji Ho Suh ◽  
Minho Shong ◽  
Hueng-Sik Choi ◽  
Keesook Lee
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Prostate Specific Antigen ◽  
Transcriptional Activation ◽  
Mrna Level ◽  
Specific Antigen ◽  
Negative Regulator ◽  
Dependent Manner ◽  
Target Promoters

Abstract CR6-interacting factor 1 (CRIF1) was previously identified as a nuclear protein that interacts with members of the Gadd45 family and plays a role as a negative regulator in cell growth. However, the nuclear function of CRIF1 remains largely unknown. In this study, we demonstrate that CRIF1 acts as a novel corepressor of the androgen receptor (AR) in prostatic cells. Transient transfection studies show that CRIF1 specifically represses AR transcriptional activation of target promoters in a dose-dependent manner. Additionally, CRIF1 is recruited with AR to the endogenous AR target promoters. In vivo and in vitro protein interaction assays reveal that CRIF1 directly interacts with AR via the activation function-1 domain of AR. Interestingly, both the N-terminal and C-terminal half-regions of CRIF1 are independently capable of interacting with and repressing the transactivation of AR. CRIF1 represses AR transactivation through competition with AR coactivators. In addition, the CRIF1-mediated inhibition of AR transactivation involves the recruitment of histone deacetylase 4. Down-regulation of CRIF1 by small interfering RNA increases the transactivation of AR and the mRNA level of the AR target gene prostate-specific antigen, whereas the overexpression of CRIF1 decreases the prostate-specific antigen mRNA level. Finally, the overexpression of CRIF1 inhibits the androgen-induced proliferation and cell cycle progression of prostate cancer cells. Taken together, these results suggest that CRIF1 acts as an AR corepressor and may play an important role in the regulation of AR-positive growth of prostate cancer.

Regulation of prostate-specific antigen by activin A in prostate cancer LNCaP cells

2004 ◽  
Vol 286 (6) ◽  
pp. E927-E931 ◽  
Author(s):  
Yasuhisa Fujii ◽  
Satoru Kawakami ◽  
Yohei Okada ◽  
Yukio Kageyama ◽  
Kazunori Kihara
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cell Growth ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Activin A ◽  
Prostate Tissue ◽  
Dependent Manner ◽  
Lncap Cells

Activins are multifunctional growth and differentiation factors and stimulate FSH-β gene expression and FSH secretion by the pituitary gonadotropes. Follistatins bind activin, resulting in the neutralization of activin bioactivity. The activin/follistatin system is present in the prostate tissue. Prostate-specific antigen (PSA) plays an important role in male reproductive physiology as well as being very important as a tumor marker for prostate cancer. Thus the regulation of PSA has important clinical implications. Previous studies showed that PSA is primarily regulated by androgens. In the present study, we evaluated the direct effects of activin A on the proliferation and PSA production of prostate cancer LNCaP cells, which express functional activin receptors and androgen receptor and PSA. LNCaP cells were treated with activin A and 5α-dihydrotestosterone (DHT) with or without their antagonists (follistatin or the nonsteroidal anti-androgen bicalutamide). Activin A decreased cell growth of LNCaP cells in a dose-dependent manner, whereas DHT increased it in a biphasic manner. In contrast to their opposing actions on cell growth, both activin A and DHT upregulated PSA gene expression and increased PSA secretion by LNCaP cells. The effects of activin A and DHT to increase PSA production were synergistic or additive. Follistatin or bicalutamide was without effect on cell growth or PSA production. The effects of activin A on LNCaP cells were blocked by follistatin, not by bicalutamide, whereas effects of DHT were prevented by bicalutamide, not by follistatin. Activin A upregulates PSA production, and the effect is through an androgen receptor-independent pathway. The activin/follistatin system can be a physiological modulator of PSA gene transcription and secretion in the prostate tissue, and activins may cooperate with androgen to upregulate PSA in vivo.

Polymorphisms in the androgen receptor and the prostate-specific antigen genes and prostate cancer risk

The Prostate ◽  
2005 ◽  
Vol 65 (1) ◽  
pp. 58-65 ◽  
Author(s):  
Claudia A. Salinas ◽  
Melissa A. Austin ◽  
Elaine O. Ostrander ◽  
Janet L. Stanford
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Risk ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Prostate Cancer Risk

scholarly journals Application of 188Rhenium as an Alternative Radionuclide for Treatment of Prostate Cancer after Tumor-Specific Sodium Iodide Symporter Gene Expression

2007 ◽  
Vol 92 (11) ◽  
pp. 4451-4458 ◽  
Author(s):  
Michael J. Willhauck ◽  
Bibi-Rana Sharif Samani ◽  
Franz-Josef Gildehaus ◽  
Ingo Wolf ◽  
Reingard Senekowitsch-Schmidtke ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Therapeutic Effect ◽  
Half Life ◽  
Sodium Iodide ◽  
Specific Antigen ◽  
Volume Reduction ◽  
Sodium Iodide Symporter ◽  
Nis Gene

Abstract Context: We reported recently the induction of iodide accumulation in prostate cancer cells (LNCaP) by prostate-specific antigen promoter-directed sodium iodide symporter (NIS) expression that allowed a significant therapeutic effect of 131iodine (131I). These data demonstrated the potential of the NIS gene as a novel therapeutic gene, although in some extrathyroidal tumors, therapeutic efficacy may be limited by rapid iodide efflux due to a lack of iodide organification. Objective: In the current study, we therefore studied the potential of 188rhenium (188Re), as an alternative radionuclide, also transported by NIS, with a shorter half-life and higher energy β-particles than 131I. Results: NIS-transfected LNCaP cells (NP-1) concentrated 8% of the total applied activity of 188Re as compared with 16% of 125I, which was sufficient for a therapeutic effect in an in vitro clonogenic assay. γ-Camera imaging of NP-1 cell xenografts in nude mice revealed accumulation of 8–16% injected dose (ID)/g 188Re (biological half-life 12.9 h), which resulted in a 4.7-fold increased tumor absorbed dose (450 mGy/MBq) for 188Re as compared with 131I. After application of 55.5 MBq 131I or 188Re, smaller tumors showed a similar average volume reduction of 86%, whereas in larger tumors volume reduction was significantly increased from 73% after 131I treatment to 85% after application of 188Re. Conclusion: Although in smaller prostate cancer xenografts both radionuclides seemed to be equally effective after prostate-specific antigen promoter-mediated NIS gene delivery, a superior therapeutic effect has been demonstrated for 188Re in larger tumors.

scholarly journals White Button Mushroom Disrupts AR Signaling in Prostate Cancer: The Scientific Basis for a Diet-Based Chemoprevention

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A820-A821
Author(s):  
Xiaoqiang Wang ◽  
Desiree Ha ◽  
Hitomi Mori ◽  
Shiuan Chen
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Agaricus Bisporus ◽  
Specific Antigen ◽  
Scientific Basis ◽  
Luciferase Assay ◽  
Dependent Manner ◽  
Button Mushroom ◽  
Western Blots ◽  
White Button Mushroom

Abstract White button mushroom (WBM) (Agaricus bisporus) is a potential prostate cancer (PCa) chemo-preventive and therapeutic agent. Our clinical phase trial of WBM powder in patients with biochemically recurrent PCa indicated that WBM intake reduced the circulating levels of prostate-specific antigen (PSA), with minimal side effects [1]. We hypothesized that WBM exerts its effects on PCa through the androgen receptor (AR) signaling axis. We thus conducted the reverse translational study. Androgen-sensitive PCa cell lines (LNCaP and VCaP) and patient-derived-xenografts (PDX), of a prostate tumor (TM00298) were used. In both LNCaP and VCaP cells, western blots and qRT-PCR assays indicated that WBM extract (6~30 mg/mL) suppressed DHT-induced PSA expression and cell proliferation in a dose-dependent manner. Immunofluorescence on AR revealed that the nuclear localization of AR was reduced upon WBM extract treatment, which agreed with the results of a PSA promotor-luciferase assay, suggesting that WBM extract inhibited DHT-induced luciferase activity. RNA-Seq on WBM-treated LNCaP cells confirmed that WBM treatment suppressed androgen response pathways and cell-cycle control pathways. Our prostate cancer PDX showed that oral intake of WBM extract (200 mg/kg/day) significantly suppressed tumor growth, as well as decreased PSA levels in both tumors and serum. Both in vitro and in vivo studies suggested that chemical(s) in WBM extract behave as AR antagonist(s). We previously identified a conjugated linoleic acid isomer (CLA-9Z11E) as an active component in WBM extract. In the present study, we extended these findings by performing LanthaScreen™ TR-FRET AR Coactivator Interaction Assays for a direct interaction of CLA-9Z11E with AR. We report here that CLA-9Z11E exerts a strong antagonist potency against the recruitment of an AR coactivator peptide towards AR. The inhibitory effect of CLA-9Z11E (IC50: 350 nM) was nearly two times stronger than the known AR antagonist, cyproterone acetate (IC50: 672 nM). The information gained from this study improves the overall understanding of how WBM may contribute to the prevention and treatment of PCa. It also serves as an important, scientific basis for developing diet-based chemoprevention and integrative therapeutic strategies for prostate cancer (supported by NIH R01 CA227230). Reference: [1] Twardowski P, et al. A phase I trial of mushroom powder in patients with biochemically recurrent prostate cancer: Roles of cytokines and myeloid-derived suppressor cells for Agaricus bisporus-induced prostate-specific antigen responses. Cancer. 2015.121(17):2942-50.

scholarly journals Walnut polyphenol metabolites, urolithins A and B, inhibit the expression of the prostate-specific antigen and the androgen receptor in prostate cancer cells

2014 ◽  
Vol 5 (11) ◽  
pp. 2922-2930 ◽  
Author(s):  
Claudia Sánchez-González ◽  
Carlos J. Ciudad ◽  
Véronique Noé ◽  
Maria Izquierdo-Pulido
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Cells ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Prostate Cancer Cells ◽  
Down Regulation

Urolithins attenuate the function of the AR by repressing its expression, causing a down-regulation of PSA levels and inducing apoptosis. Our results suggest that a diet rich in ellagitannins could contribute to the prevention of prostate cancer.

Sign in / Sign up

Export Citation Format

Share Document