Prostate cancer is the second most common cancer among men in the United States, and y the causes of prostate cancer are unknown. Human prostatic acid phosphatase (PACP) is differentiation antigen in prostate epithelial cells. Most prostate carcinomas are poorly differentiated and have a repressed expression of cellular PACP, however the secretory form PACP serves as a marker for the diagnosis of the cancer. The regulation of expression of PA isoenzymes and their possible physiological function are not understood. Our long term goal is to delineate the mechanism of malignant growth of prostate cells. Because of the close association of cellular PACP expression with the differentiation of prostate cells and its inverse correlation to cell growth rate, we are going to delineate the regulation of PAcP expression. Our working hypothesis is that understanding the regulation and the possible function PACP will lead us to understand the biology of prostate cancer. The major goal of this proposal is to clarify the regulation by androgen and the possible role cellular PAcP in prostate epithelial cells.
The Specific Aims are to: 1) Determine the regulation of expression of PACP isozymes by androgens at the post-translational level in prostate cells. We will further examine whether the expression of cellular PACP levels inversely correlate to the growth rate of cans. 2) Compare the gene expression and gene structure of PACP in cancer cans with normal ce by Northern and Southern blot analyses with PACP CDNA probes. We will clarify whether androgen regulates PACP gene expression at the transcriptional level by Northern blotting. 3) Compare molecular structures of PACP isoenzymes by two-dimensional peptide mapping analysis. We will characterize PACP isoenzymes for phosphotyrosyl (p-tyr) phosphatase activity with phosphoprotein substrates. We will also determine whether PACP is a phosphoprotein and if its specific activity is regulated by phosphorylation and dephosphorylation. 4) Identify the putative phosphoprotein(s) whose phosphorylation state is increased while cellular PACP activity is inhibited. Understanding the regulation of PACP and its possible function may lead us to understand the malignant growth of prostate cells which may result in improving the therapy of the cancer.
