The long-term goals are to study growth regulation of the human prostate and to understand why in middle-age the prostate starts to grow in most men to cause the obstructive and other symptoms of benign prostatic hyperplasia (BPH). In this project the aims are firstly to identify and isolate epithelial stem cells from biopsies of normal prostate from young men and BPH from older men, and secondly to conditionally immortalize both epithelial stem and mesenchymal cells from the same individuals. Prostate stem cells have not yet been characterized or isolated. In normal tissue, stem cells are important in cell proliferation and homeostasis because they provide for cellular self-renewal. In disease, stem cells are important because changes in the regulation of their growth may be the cause of benign proliferative disorders such as BPH. Conditional immortalization of epithelial stem and mesenchymal cells using a temperature-sensitive gene in a retroviral vector will have two advantages. Firstly, it will enable the cloning and selection of epithelial and mesenchymal cells which retain the characteristics of prostate tissue; and secondly, it will permit the modulation of cell growth and differentiation using the temperature control. These advantages are important because none of the cell lines derived from human prostate that are currently available express all of the essential characteristics of prostate cells. In addition, there are no paired epithelial and mesenchymal cell lines from the same individual, and thus having the same genetic background. Such lines will provide a valuable resource for scientists studying the prostate because the development and function of the prostate are known to be regulated by reciprocal interactions between the epithelium and the mesenchyme.
