application) The overall objective of the proposed research is to gain insight into the pathogenesis of benign prostatic hyperplasia (BPH) by applying basic research tools developed in UT Southwestern?s O?Brien Center Research program to the carefully characterized BPH biopsy tissue obtained in the NIH-funded BPF clinical trial (MTOPS). Analysis of prostate tissue and clinical data obtained longitudinally during the course of the five year MTOPS trial can be utilized to characterize the role of specific cellular factors or the development and progression of clinical BPH. The clinical trial endpoints of prostate growth (determined by ultrasound) and time to clinical progression (worsening symptoms) can be correlated with changes in prostatic histology and concomitant alterations in prostate gene expression. The following specific aims will be developed: 1) determine the feasibility of assaying specific gene and protein expression in thin sections of prostate biopsy material; 2) determine if localized increases in stromal cell 5alphareductase type 2 expression correlate with localized epithelial cell proliferation; 3) determine the relationship between epithelial cell mass, prostate growth rate and response to androgen withdrawal therapy; 4) using DOC2 as a marker of basal cell differentiation in the prostate, determine whether hyperplastic growth is associated with basal cell de-differentiation and proliferation; 5) to determine whether locally increased expression of specific FGF-family growth factor correlate with increased rates of prostatic growth.
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