The major objective of this research is to understand the molcular basis of regionalization of the prostate gland. A prominent but poorly understood feature of diseases that afflict the human prostate is their region-specific nature. We propose to characterize genes that are regionally expressed during the process of branching morphogenesis that gives rise to the mature mouse prostate gland. Our preliminary studies have identified a novel androgen-responsive prostate-specific gene that is predominantly expressed in one lobe in the early postnatal period. Expression of this gene is dramatically down-regulated in mouse prostate tumors To examine the molecular basis of regional prostate gene expression, we propose to identify the cis-regulatory elements that mediate this pattern of expression using a reporter gene approach in transgemc mice. We further propose to characterize the proteins that bind to these elements to regulate their activity in vivo. The successful completion of this work will generate new insights into the molecular basis of prostate morphogenesis in the mouse that may greatly enhance our understanding of human prostate disease.
| McMullin, Ryan P; Dobi, Albert; Mutton, Laura N et al. (2010) A FOXA1-binding enhancer regulates Hoxb13 expression in the prostate gland. Proc Natl Acad Sci U S A 107:98-103 |
| McMullin, Ryan P; Mutton, Laura N; Bieberich, Charles J (2009) Hoxb13 regulatory elements mediate transgene expression during prostate organogenesis and carcinogenesis. Dev Dyn 238:664-72 |
| Chen, Hui; Mutton, Laura N; Prins, Gail S et al. (2005) Distinct regulatory elements mediate the dynamic expression pattern of Nkx3.1. Dev Dyn 234:961-73 |
