The prostate gland is the most diseased organ in the human body. A striking feature of prostate biology is that different diseases are typically confined to only one region of the prostate gland such that the peripheral zone accounts for nearly all cases of prostate cancer while benign prostatic hyperplasia is restricted to the transition zone. There is a paucity of information on the molecular basis of prostate regionalization and patterning. In an effort to elucidate the cellular and molecular mechanisms that underlie initiation and maintenance of normal prostate growth, with a long-term view towards understanding the basis of human disease susceptibility, we propose a comprehensive study of regional gene expression in developing prostate glands. Using the mouse as a model system, where zones (termed lobes) are readily dissected, I propose to use a genomic approach to identify genes that are locally expressed during prostate growth and differentiation. A preliminary survey employing differential display analysis has covered approximately 20% of all transcribed genes and identified a number of candidate genes that are region-specific. Further characterization of these genes and their roles in prostate development and differentiation may yield insights into the molecular basis of normal prostate development as well as prostate disease.
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