BIOLOGY OF HUMAN PROSTATE CANCER

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.