The chicken ovalbumin upstream promoter-transcription factor II negatively regulates the transactivation of androgen receptor in prostate cancer cells

PLoS One. 2012;7(11):e49026. doi: 10.1371/journal.pone.0049026. Epub 2012 Nov 7.

Abstract

Androgen receptor (AR) is involved in the development and progression of prostate cancers. However, the mechanisms by which this occurs remain incompletely understood. In previous reports, chicken ovalbumin upstream promoter-transcription factor II (COUP-TF II) has been suggested to play a role in the development of cancers. In the present study, we explored a putative role of COUP-TF II in prostate cancers by investigating its effect on cell proliferation and a cross-talk between COUP-TF II and AR. Overexpression of COUP-TF II results in the inhibition of androgen-dependent proliferation of prostate cancer cells. Further studies show that COUP-TF II functions as a corepressor of AR. It represses AR transactivation on target promoters containing the androgen response element (ARE) in a dose-dependent manner. In addition, COUP-TF II interacts physically with AR in vitro and in vivo. It binds to both the DNA binding domain (DBD) and the ligand-binding domain (LBD) of AR and disrupts the N/C terminal interaction of AR. Furthermore, COUP-TF II competes with coactivators such as ARA70, SRC-1, and GRIP1 to modulate AR transactivation as well as inhibiting the recruitment of AR to its ARE-containing target promoter. Taken together, our findings suggest that COUP-TF II is a novel corepressor of AR, and provide an insight into the role of COUP-TF II in prostate cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • COUP Transcription Factor II / genetics*
  • COUP Transcription Factor II / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • Chlorocebus aethiops
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Male
  • Mice
  • Promoter Regions, Genetic
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism*
  • Protein Transport
  • Receptors, Androgen / genetics*
  • Receptors, Androgen / metabolism*
  • Transcription, Genetic
  • Transcriptional Activation

Substances

  • COUP Transcription Factor II
  • DNA-Binding Proteins
  • Receptors, Androgen

Grant support

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012–0085). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.