Interest in understanding the biology of the prostate gland is motivated by the high incidence in humans of prostatic diseases including prostatic adenocarcinoma and benign prostatic hyperplasia. One crucial but poorly understood aspect of prostate biology is the molecular basis for region specific identity within the prostate. Nevertheless, this aspect of prostatic biology is important because prostatic diseases occur in a highly region-specific manner with prostatic adenocarcinoma predominantly a disease of the peripheral zone and benign prostatic hyperplasia predominantly a disease of the transition zone. It is also clear that both epithelial region-specific identity and the progression of prostatic adenocarcinoma are influenced by paracrine signals from the prostatic stroma. In recent years, the mouse has become an increasingly important model system for understanding prostatic biology and modeling prostatic diseases. Prostate-specific promoters and enhancers have facilitated this area of research. However, the characterized prostate-specific promoters and enhancers are not adequate to explore all aspects of prostatic development and disease. Our preliminary studies have established a new and efficient method to screen for promoter and enhancer elements that direct gene expression in a region-specific manner in the prostate gland. Work described in Aim 1 of this proposal will use this new approach to identify and characterize promoter and enhancer elements associated with two genes that are expressed in prostatic cell types not accessible with currently available promoter or enhancer elements. One gene is expressed specifically in epithelial cells of the anterior and dorsal prostate. The second gene is expressed in prostatic stromal cells. Work described in Aim 2 of this proposal will use the newly defined regulatory elements to create lines of transgenic mice expressing CRE recombinase in prostatic cell types not covered by currently available CRE transgenic lines.
| Joesting, Margaret S; Cheever, Thomas R; Volzing, Katherine G et al. (2008) Secreted frizzled related protein 1 is a paracrine modulator of epithelial branching morphogenesis, proliferation, and secretory gene expression in the prostate. Dev Biol 317:161-73 |
| Lange, Carol A; Gioeli, Daniel; Hammes, Stephen R et al. (2007) Integration of rapid signaling events with steroid hormone receptor action in breast and prostate cancer. Annu Rev Physiol 69:171-99 |
| Thielen, Joshua L; Volzing, Katherine G; Collier, Lara S et al. (2007) Markers of prostate region-specific epithelial identity define anatomical locations in the mouse prostate that are molecularly similar to human prostate cancers. Differentiation 75:49-61 |
