Our recent studies indicate that there is a regional variation in morphologic and functional activities in the prostatic ductal system. In the present study, we postulate that the observed regional variation in the prostatic ductal system is mediated by a regional variation in androgen responsiveness through a locally manifested cell-to-cell interaction. The following specific aims are proposed:
SPECIFIC AIM 1 will study the impact of prostatic stromal cells on epithelial cells. Two major cell types in the stroma are fibroblasts and smooth muscle cells. We will further refine our methodology on separation and culture of these cells from the adult rat prostate, investigate types of growth factors produced by these cells, and test the effect of these growth factors on prostatic epithelial cells.
SPECIFIC AIM 2 is to investigate the action of androgen in the prostate. We will attempt to test the possibility that DHT is directly acting in the epithelial cells to promote differentiation, using prostatic binding protein (PBP) as the marker protein for cellular differentiation. On the other hand, we postulate that epithelial proliferation is stimulated indirectly by DHT through the production of growth factors from the stromal cells.
SPECIFIC AIM 3 will study the impact of epithelial cells on stromal cells through a paracrine mechanism. We will test the possibility of whether epithelial cells will secrete growth factors which directly impact on stromal cells, and investigate the effect epithelial cells have on the fate of uncommitted prostatic mesenchymal cells and on functional activities of fibroblasts and smooth muscle cells.
SPECIFIC AIM 4 is to test the possibility that basal cells are the precursor cells in the rat prostate. We will use specific antibodies for basal cell cytokeratin (MA 903), luminal cells (RGE 53), and PBP antibody to identify cells which are intermediary between basal cells and luminal cells. We will use the developing prostate as the model system for the present study. Results of this proposed study will have significant clinical implications regarding the etiology of prostatic disease because a deviation from the normal programming of cell-to-cell interaction may lead to abnormal control of prostatic growth, as seen in benign prostatic hyperplasia and prostate cancer.
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