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Submitted on January 4, 2002
Accepted on July 5, 2002
1 Departments of Urology, Biological Chemistry, Medicineand Molecular Biology Institute, UCLA School of Medicine, Los Angeles CA 90095
* To whom correspondence should be addressed. E-mail: mcarey{at}mednet.ucla.edu.
Prostate stem cell antigen (PSCA) is emerging as an important diagnostic marker and therapeutic target in prostate cancer. Previous studies indicated that prostate stem cell antigen was directly regulated by androgens but the mechanism has not been elucidated. Here we describe the identification of a compact cell-specific and androgen-responsive enhancer between 2.7 and 3 kb upstream of the transcription start site. The enhancer functions autonomously when positioned immediately adjacent to a minimal promoter. DNase I footprinting analysis with recombinant androgen receptor (AR) reveals that the enhancer contains two androgen receptor binding sites at one end. Mutational analysis of the androgen receptor binding sites revealed the importance of the higher affinity one. The dissociation constant (Kd) of the high affinity binding site (AREI) was determined to be 
87 nM. The remainder of the enhancer contains elements that function synergistically with the androgen receptor. We discuss the structural organization of the PSCA enhancer and compare it to that found in other AR-regulated genes.
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