EXPRESSION AND LOCALIZATION OF ACTIVIN SUBUNITS AND FOLLISTATINS IN TISSUES FROM MEN WITH HIGH-GRADE PROSTATE-CANCER

Activins are growth and differentiation factors that have growth inhib itory effects on LNCaP and DU145, but not PC3, human prostate tumor ce ll lines. Activin-binding proteins, follistatins, block the inhibitory actions of exogenously added activins on LNCaP and DU145 tumor cell L ines. Based on these in vitro observations using human prostate tumor cell lines, the aims of this study were to determine whether activins and follistatins are expressed in the human prostate in tissues from m en with high grade prostate cancer. The expression and cellular locali zation of these proteins in malignant and nonmalignant regions of thes e tissues were compared to determine whether any changes occur with pr ogression to malignancy. The results demonstrate that activins and fol listatins are synthesized in tissues from men with high grade prostate cancer, and that messenger ribonucleic acid (mRNA) and protein for th e activin beta A- and beta(B)-subunits and follistatin is expressed an d localized to poorly differentiated tumor cells. In the nonmalignant regions, activin beta(A) and beta(B) subunit mRNA and proteins are pre dominantly localized to the epithelium. Follistatin mRNA was expressed in the basal epithelial cells and in the fibroblastic stroma; however , the localization of follistatin proteins using two specific antisera demonstrated a difference between the follistatin isoforms expressed in basal cells and the stroma. In the progression to malignancy, the c olocalization of follistatin and activins to the tumor cells in vivo i mplies that resistance to the growth inhibitory effects of activin may be conferred by follistatins.