Abstract B2: Coup-tf1 is suppressed by androgen receptor in prostate cancer epithelial and normal stromal cells

Abstract

Abstract Chicken ovalbumin upstream promoter-transcription factor 1 (Coup-tf1) is a transcription repressor previously known to play a role in neurogenesis and adipogenesis. It mainly acts through suppression of thyroid hormone receptor and vitamin D receptor. Coup-tf1 was implicated before in breast cancer as a negative regulator of the Aromatase gene, and in gastric cancer cell lines as a positive regulator of vegf-d. We performed a genome wide location analysis of androgen receptor (AR) target genes in prostate cancer cells treated with androgen, an AR antagonist or androgen deprivation. This analysis revealed ligand dependent binding of the coup-tf1 promoter and enhancer by the AR which was confirmed by specific chromatin immunoprecipitation studies. AR activation by a ligand is correlated with decreasing mRNA levels implying that AR is a negative regulator of coup-tf1 in prostate cancer cells. Using immunohistochemistry we have seen coup-tf1 staining in 21/28 primary human prostate cancer samples, regardless of Gleason score or prognosis. Coup-tf1 staining was in a nucleolar pattern and its levels in malignant cells were substantially higher than in the adjacent benign prostate glands. Stromal cells both in human and mouse prostate show nuclear coup-tf1 staining. There is an inverse correlation between Coup-tf1 staining and the rising levels of androgen with advancing puberty. These results implicate coup-tf1 in prostate cancer for the first time, and show a novel AR repressed gene, that might play a role in prostate cancer. Citation Information: Cancer Res 2009;69(23 Suppl):B2.