Arginase: A Novel Proliferative Determinant in Prostate Cancer.

摘要

This project is an investigation of the involvement of the enzyme arginase type II (AII) in the pathogenesis and growth of prostate cancer. Having cloned the AII gene in our laboratory, we unexpectedly discovered that is expressed at high levels in the normal prostate and even higher in neoplastic prostate samples. The purpose of the present research funded by USAMRMC is to examine the expression of AII in a wider range of benign and malignant prostate specimens and cultured cells to determine its usefulness as a novel marker of prostatic neoplasia and the extent of its involvement in cancer pathogenesis. We are also exploring whether specific chemical and molecular inhibitors of arginase and several related enzymes in the polyamine metabolic pathway might suppress or arrest the growth of prostate cancer cells in vitro or in vivo. This fourth annual report describes our progress over the past year in extending our characterization of arginase and other related enzymes in two new prostate cancer cell lines to address the possibility of AII and androgen susceptibility, correlating polyamine synthesis in all of the prostate cancer cell lines with AII and OAT expression, examining expression levels of polyamine biosynthetic enzymes in these cell lines, creating stable cell lines expressing AII siRNA and overexpression constructs, determining AII expression in the various prostate histological categories of a tissue microarray, and assessing genito-urinary (GU) weights for the proposed in vivo TRAMP studies.