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.

Carcinogenesis
|October 10, 2013
PubMed

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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