Abstract

We have isolated several human androgen receptor (AR)-associated factors by protein-protein interaction screening; sequences of the cDNA were determined and deposited in Gene bank. Subsequently, another group has identified the locus of one hereditary prostate cancer factor (HPCF) implicated in hereditary prostate cancer (HPC). From human prostate cancer cells, several mutants of HPCF were isolated and we now report the molecular characterization of this factor. Using molecular biology tools, we have identified a novel human tumor-specific HPCF that associates with the N-terminal activation function (AF-1) of the human androgen receptor. Direct and indirect immunofluorescence studies showed that HPCF was primarily localized in the cytoplasm of human prostate cancer cells and breast tumor cells. There are three different translation products of HPCF expressed in various cancer cells. One of these products activated AR-mediated transcription of a model gene in a constitutive manner, thus implicating it in a ligand-independent modulation of androgen receptor to promote prostate cancer growth.