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Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
Published on: November 15, 2013
The orphan receptor ERRalpha interferes with steroid signaling
Catherine Teyssier1, Stéphanie Bianco, Olivia Lanvin
1Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, CNRS, INRA, 69364 Lyon cedex 07, France.
Nucleic Acids Research
|August 14, 2008
Summary
Estrogen receptor-related receptor alpha (ERRalpha) influences androgen signaling in prostate cells. Targeting ERRalpha impacts androgen-responsive genes and prostate-specific antigen (PSA) promoter activity.
Area of Science:
- Endocrinology
- Molecular Biology
- Cancer Research
Background:
- Estrogen receptor-related receptor alpha (ERRalpha) is an orphan nuclear receptor.
- ERRalpha is known to interfere with estrogen signaling pathways.
- Steroid hormone signaling pathways are crucial in various physiological processes, including cancer development.
Purpose of the Study:
- To investigate the cross-talk between ERRalpha and signaling pathways of other steroid hormones, specifically androgens.
- To determine the effect of ERRalpha modulation on androgen-responsive genes and promoters in human prostatic cells.
Main Methods:
- Utilized a specific ERRalpha inverse agonist for treatment of human prostatic cells.
- Analyzed the expression of androgen-responsive genes.
- Investigated the activation of androgen response elements (ARE)-containing promoters, including the PSA promoter.
- Examined the impact of antisteroid compounds on ERRalpha-mediated activation.
Main Results:
- Treatment with an ERRalpha inverse agonist reduced the expression of several androgen-responsive genes without affecting androgen receptor (AR) expression or activity.
- ERRalpha was found to activate ARE-containing promoters, such as the PSA promoter, in an ARE-dependent manner.
- All members of the ERR orphan receptor subfamily could activate promoters with steroid response elements, even in the presence of antisteroid compounds.
Conclusions:
- ERRalpha plays a significant role in modulating androgen signaling in prostate cells.
- Targeting ERRalpha presents a potential therapeutic strategy for prostate conditions involving androgen signaling.
- The ERR subfamily of orphan receptors exhibits broad activity on steroid hormone response elements.
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