This is a revised application that was originally submitted in response to the RFA on """"""""The Regulation of Prostate Growth"""""""". The goal of this proposal is to identify novel genes which control normal growth, differentiation and function of stem cells in the human prostate.
In Specific Aim 1, the principal investigator will use subtractive hybridization techniques (representational difference analysis or RDA), to identify candidate stem cell genes in the prostate, essentially by subtracting cDNA of normal prostate basal epithelial stem cells from normal prostate secretory cells.
In Specific Aim 2, each RDA product will be subjected to a well-defined algorithm analysis that includes extensive automated sequencing, and expression profile based on Northern analysis and in situ hybridization. This will provide the initial """"""""filtering mechanism"""""""" for the selection of basal cell specific candidate genes. Once the candidate genes will be thus identified, studies proposed in Specific Aim 3 will focus on the biological effects of these stem cell specific genes on prostatic growth and differentiation. Full length cDNAs will be introduced into human prostate and rat prostate cells, by retroviral infection, in order to determine the effect of these novel genes on various biological characteristics of stem cell function such as androgen-independence, resistance to apoptosis and ability for self-renewal. These studies will enhance our understanding of the potential role of prostatic stem cell population in the normal and abnormal growth of the prostate that characterizes benign prostatic hypertrophy.
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