Identification of Signaling Proteins the Modulate Androgen Receptor Activity

摘要

Androgens and the androgen receptor (AR) play a critical role in the development and progression of prostate cancers. The majority of prostate cancers initially respond to endocrine treatment (androgen dependent), but eventually become androgen independent that prove fatal. It appears that a functionally active AR may contribute to the progression of androgen- independent prostate cancers. Understanding the signaling pathways that regulate androgen-dependent and - independent activation of AR mediated transcription would provide valuable information for finding an ultimate cure for this disease. We have proposed to identify the signaling components that regulate AR activity using a novel retrovirus- mediated genetic system, and to understand the mechanism of how the identified factors control AR activity. To this end, we have established and optimized our retrovirus-mediated genetic screen approach. The retroviral vectors to be used have been improved which will allow high-efficiency mutagenesis and ease of manipulation and analysis. We have also made significant progress towards optimizing our screening strategies and establishing a suitable cell line for the genetic screen. With these tools in hand, we are in the process of performing the genome wide genetic screen to identify genes that are important for androgen receptor signaling and study how they may contribute to the progression of prostate cancers.