Gene expression profiling in the developing prostate

Abstract

Gene expression profiling has proven to be an effective tool for characterizing genes and molecular pathways operative at key stages of organogenesis. Temporal profiling of RNA transcripts can provide valuable insights into mechanisms of differentiation and lay a foundation for characterizing molecular aspects of development. Descriptive and functional experiments have demonstrated critical roles for androgenic hormones and mesenchymal-epithelial interactions during prostate organogenesis. These studies have uncovered roles for members of several growth factor pathways--primarily using a candidate gene approach--but it is likely that critical molecular determinants of prostate organogenesis remain to be defined. Despite the potential for expression profiling to uncover novel genes and pathways, only a limited number of gene profiling studies have focused on the developing prostate. Among these are studies based on the generation of cDNA libraries and expressed sequence tags (ESTs) and other tag counting strategies such as serial analysis of gene expression (SAGE). Recently, microarray-based assays have provided more comprehensive time-course studies of molecular pathways associated with induction, branching morphogenesis, and secretory differentiation. Several profiling methods have also been used to characterize the influences of androgenic hormones on different tissue compartments including the urogenital sinus mesenchyme (UGM) and urogenital sinus epithelium (UGE) in order to define paracrine mediators operative in early morphogenesis. While hypothesis-driven candidate gene studies remain the gold standard for delineating cause-and-effect relationships dictating the complex biological regulators of the developing prostate, gene profiling provides a valuable adjunct, and is especially useful as an unbiased first step for generating new hypotheses. This review will focus on detailing the methods and results of profiling strategies in the context of normal prostate gland development, with implications for alterations in conserved pathways that may contribute to prostatic diseases.