title: The chicken ovalbumin upstream promoter-transcription factor II negatively regulates the transactivation of androgen receptor in prostate cancer cells.
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.
authors.affiliation: Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Chin-Hee
authors.initials: CH
authors.lastname: Song
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Lee
authors.forename: Eunsook
authors.initials: E
authors.lastname: Park
authors.forename: Keesook
authors.initials: K
authors.lastname: Lee
mesh_terms: D000818:Animals; D019556:COS Cells; D051837:COUP Transcription Factor II / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism*; D021381:Protein Transport; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D051837:COUP Transcription Factor II; D004268:DNA-Binding Proteins; D011944:Receptors, Androgen