Mechanism and Regulation of Gene Expression by Androgen Receptor in Prostate Cancer
Abstract
Our general objective is to use completely defined cell-free transcription systems both to identify novel AR-associated cofactors and to investigate the mechanism of action of AR and both novel and previously identified candidate coactivators. To this end, we have expressed and purified 5 AR-associated cofactors and established a chromatin assembly system to study AR function with chromatin template. We have shown an enhancement of AR function by the TRAP/Mediator coactivator complex that is generally utilized by a number of different nuclear receptors. Relevant to the mechanism involved, we have identified two TRAP/Mediator subunits as potential targets for the liganded AR receptor. The expression of AR and 10 cofactors by quantitative in situ RNA hybridization in 44 primary prostate cancers with different degree of differentiation was investigated. Our results revealed near constant expression of AR and heterogeneous expression of AR cofactors. Expression of PIAS1 and Ran/ARA24 was increased and expression of ELEl/ATRA70 was decreased. In addition, we demonstrated that the human prostate tumor cell proliferation and colony formation are markedly reduced by over-expression of ELEl/ARA70. Together, these findings indicate that the change of expression levels of AR cofactors may play important roles in prostate growth and tumorigenesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA410218
Entities
People
- Hua Wang
- Keiko Hosohata
- Zhengxin Wang
Organizations
- The University of Texas MD Anderson Cancer Center