An efficient procedure for cloning hormone-responsive genes from a specific tissue

Nuclear receptors form a superfamily of ligand-activated transcription fact ors. In contrast to the significant advances made in recent years to dissec t nuclear receptor structure and their corresponding function, progress has been rather slow in the identification of target genes for nuclear recepto rs, information that is a prerequisite for understanding hormone action. He re, we describe a simple screening protocol that makes it possible to effic iently and effectively clone hormone-responsive genes that are specific to a tissue of interest, When this procedure was used to clone prostate-specif ic and androgen-responsive genes, approximately 40% of the clones selected at random represented genes that are known to be androgen regulated and are largely specific to prostate for expression, such as prostate specific ant igen (PSA). A further 37% are known to be highly enriched in prostate for e xpression, but their androgen regulation is yet to be studied, The rest of the clones represented novel genes, expressed sequence tags, or known genes whose possible androgen regulation has not yet been assessed. This screeni ng scheme can be applied to any hormone/ligand to clone differentially expr essed genes specific to a tissue of interest. Identification of such genes and their characterization should greatly facilitate understanding hormone action in normal and pathological conditions.