Regulation of AR Expression and Function By Nur77 in Prostate Cancer Cells

Presentation Number: SUN 260
Date of Presentation: April 2nd, 2017

Tuyen Thanh Tran*1 and Keesook Lee2
1Chonnam National University, Gwangju, Korea, Republic of (South), 2School of Biological Sciences and Biotechnology,Chonnam National University, Gwangju, Korea, Republic of (South)

Abstract

Nuclear receptor subfamily 4 group A (NR4A) includes NR4A1 (Nur77), NR4A2 (Nurr1) and NR4A3 (Nor1) and has a role in cancer development as well as multiple physiological and pathological roles. The dysregulation of NR4As was reported in many cancer types. NR4A receptors can promote or suppress tumor growth depending on specific cellular context. The level of Nur77 protein was reported to be induced by androgen and apoptotic stimuli in prostate cancer cells. Moreover, Nur77 is more highly expressed in prostate cancer areas than in adjacent normal or benign prostate hypertrophic tissue. Because androgen receptor (AR) activity and its signaling system play a pivotal role in the development and progression of prostate cancers and an interaction between Nur77 and AR has been previously reported, we hypothesize that Nur77 regulates prostate cancer development via alteration of AR signaling and AR-target gene expression. In this study, we found that Nur77 regulates AR and AR-target gene expression in prostate cancer cells. Further it also modulates the transcriptional activity of AR. Silencing of Nur77 by using siRNA targeting Nur77 in prostate cancer cells causes changed expression of both AR and AR-target genes, supporting the above findings. These results suggest that Nur77 acts as an important regulator for AR expression and activity in prostate cancer cells. Taken together, Nur77 can be an alternative target for developing of new agents for prostate cancer therapy.

 

Nothing to Disclose: TTT, KL