IDENTIFICATION OF 2 NOVEL CIS-ELEMENTS IN THE PROMOTER OF THE PROSTATE-SPECIFIC ANTIGEN GENE THAT ARE REQUIRED TO ENHANCE ANDROGEN RECEPTOR-MEDIATED TRANSACTIVATION

A monomeric androgen responsive element (ARE) is not sufficient to med iate significant androgen induction of the prostate-specific antigen ( PSA) gene, Co-transfection experiments using a series of 5' deletion f ragments of the proximal promoter region of the PSA gene linked to bac terial chloramphenicol acetyltransferase (CAT) as a reporter have iden tified two motif sequences which are indispensable for androgen recept or (AR)-mediated transactivation of the PSA promoter and have been des ignated as motifs A and B respectively, Of note, motif B alone has ver y little independent enhancer activity regardless of the presence or a bsence of androgen, whereas multi-copies of motif A exert androgenic i nducibility for a heterologous promoter independent of the presence of ARE, Nucleotide substitutions in either motif significantly decrease the androgen inducibility and the nuclear protein binding ability, Fur thermore, gel band shift experiments consistently demonstrate that nuc lear proteins can bind these motifs, and they are non-receptor factors , Our data indicate that these two DNA motifs are novel cis-regulatory elements and exhibit different mechanisms in cooperation with ARE for AR-mediated transactivation.