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Updated: May 7, 2026

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
Published on: November 15, 2013
Cooperative behavior of the nuclear receptor superfamily and its deregulation in prostate cancer
Mark D Long1, James L Thorne, James Russell
1Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
Abstract:
The current study aimed to assess the topology of the nuclear receptor (NR) superfamily in normal prostate epithelial cells and its distortion in prostate cancer. Both in vitro and in silico approaches were utilized to profile NRs expressed in non-malignant RWPE-1 cells, which were subsequently investigated by treating cells with 132 binary NR ligand combinations. Nine significant cooperative interactions emerged including both superadditive [22(R)-hydroxycholesterol and eicosatetraenoic acid] and subadditive [1α,25(OH)2D3 and chenodeoxycholic acid] cellular responses, which could be explained in part by cooperative control of cell-cycle progression and candidate gene expression. In addition, publicly available data were employed to assess NR expression in human prostate tissue. Common and significant loss of NR superfamily expression was established in publicly available data from prostate tumors, in part predicting parallel distortion of targeting microRNA. These findings suggest that the NR superfamily in the prostate cooperatively integrates signals from dietary, hormonal and metabolic cues, and is significantly distorted in prostate cancer.
Insights
Prostate cancer distorts the nuclear receptor (NR) superfamily, which normally integrates dietary and metabolic signals. This study reveals significant NR expression loss in tumors, impacting cell function and predicting microRNA changes.
Area of Science:
- Molecular Biology
- Oncology
- Cell Biology
Background:
- The nuclear receptor (NR) superfamily plays crucial roles in cellular signaling.
- Understanding NR superfamily topology in normal prostate cells is key to identifying cancer-related alterations.
Purpose of the Study:
- To investigate the structure of the NR superfamily in normal prostate epithelial cells.
- To determine how this structure is altered in prostate cancer.
Main Methods:
- Utilized in vitro and in silico methods to profile NRs in RWPE-1 cells.
- Treated cells with 132 binary NR ligand combinations to identify cooperative interactions.
- Analyzed publicly available data for NR expression in human prostate tumors and microRNA targeting.
Main Results:
- Identified nine significant cooperative NR interactions, including superadditive and subadditive responses.
- Observed a common and significant loss of NR superfamily expression in prostate tumors.
- Found that NR expression loss in tumors correlates with distorted targeting microRNA expression.
Conclusions:
- The NR superfamily in the prostate integrates dietary, hormonal, and metabolic signals.
- Prostate cancer significantly distorts NR superfamily topology and function.
- NR alterations in cancer may impact cell-cycle progression and gene expression.
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