The cellular and molecular biological role of activin-A, a molecule recently found to be localized immunohistochemically and transcribed in a cell line of prostatic cancer, DU-145, will be studied in vivo and in vitro using techniques of in situ hybridization, Northern blotting analysis, and reverse transcription-polymerase chain reaction (RT-PCR). In addition, we will study the detailed biology of prostatic activin- A/inhibin in rats during development, under hormonal manipulation, as well as in primary cultures of epithelial cells or stromal cells because inhibin/activin-A was immunohistochemically localized in intact rat prostate. We will also attempt to investigate prostatic activin-A in cell lines of other human prostatic cancers. From the data obtained with all of these approaches, we will have a baseline of fundamental information about the role of activin-A/inhibin in prostatic cancer. This knowledge will enable us to explore the role of activin-A/inhibin as growth factors in growth and differentiation of the prostate and will be clinically useful in designing new approaches to treating prostatic cancer.