The androgen receptor (AR) is a member of the nuclear hormone receptor family and plays a central role in the development of the normal prostate and in prostate cancer. The observations from androgen ablation treatment of prostate cancer have indicated that signals mediated through the AR are critical for prostate cancer growth and that alterations both in the AR and its associated proteins may contribute to primary and androgen independent prostate cancer. Understanding the mechanisms through which the AR regulates gene expression should, therefore, provide insight into abnormalities which may contribute to the development of prostate cancer and provide possible targets for future treatment. Recent reports have shown that nuclear hormone receptors must function by directly or indirectly making contacts with other transcriptional factors which include activators, repressors and modulators to mediate the effects on transcription. The major goal of this work is to identify and characterize the proteins which associate with the AR to mediate and/or modulate the effects of the AR on cell growth. The preliminary studies have provided evidence to demonstrate that an AR associated DNA binding protein complex plays a role in the process of AR regulated transcription. This proposal is to biochemically and functionally characterize this AR associated protein complex in detail to determine how it regulates the expressions of two human AR target genes, prostate specific antigen (PSA) and kallikrein 2 (KLK2). The long term goal is to define interactions between the AR and associated proteins in prostate cancer and determine whether these associated proteins can be targeted for the development useful drugs in the treatment of prostate cancer.
