REGULATORY MECHANISMS OF PROSTATE TUMOR PROGRESSION

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Abnormal conditions of the prostate constitute a major medical problem in the United States. Prostatitis, Benign enlargement (BPH), and malignant growth of the prostate (CaP) will effect the lives of most men over the age of 65. BPH is a bothersome abnormal growth that fortunately is readily treated by a variety of options. Prostatic cancer, if detected early is curable, but metastatic disease can be fatal as there is no currently available curative therapy for metastatic prostatic cancer. In addition, because of the extreme heterogeneity with regard to biologic potential of prostatic cancer there is debate on the best approach to therapy even with localized disease. There is a lack of consensus and viable approaches to management and therapy. This reflects our lack of knowledge of the biologic determinants responsible for this spectrum of behavior at a level that would provide appropriate therapeutic intervention. This O'Brien Urology Center Proposal will focus its attention on determining changes in the cellular phenotype that is associated with the progression of disease from normal to premalignant lesions to localized cancer to distant disseminated cancer. In this initial application we will focus on three areas related to growth factor associated programming in the malignant transformed phenotype. Project One will examine the alterations in tyrosine kinase associated growth factors, Project Two will examine alterations in PKC isoenzymes signal pathways in progression, and Project Three will examine the transferrin receptor like prostate specific membrane antigen PSM and transferrin receptor in prostatic tumor progression. These projects and related projects which will be identified and recruited to the Center will with time provide an understanding of the biology of progression of CaP and develop strong rationales for new interventional strategies.