EXPRESSION OF TRANSFORMING GROWTH-FACTOR-ALPHA AND THE EPIDERMAL GROWTH-FACTOR RECEPTOR IN HUMAN PROSTATE TISSUES

Cells respond to certain soluble factors that bind to cell surface rec eptors possessing intrinsic tyrosine kinase activity. Overexpression o f these molecules has been associated with tumor progression. Enhanced prostatic cancer cell growth in vitro has been reported in the presen ce of certain growth factors. To characterize the patterns of expressi on of the epidermal growth factor receptor (EGFr) and transforming gro wth factor-alpha (TGF alpha), we studied tissue from 107 prostate spec imens using immunohistochemistry. We observed that epithelial cells of normal (n = 4) and benign prostatic (n = 56) tissues express EGFr but were unreactive for TGF alpha, while stroma cells in these tissues ex press TGF alpha but not EGFr. However, coexpression of EGFr and TGF al pha was identified in 22 of 46 prostatic adenocarcinomas studied. Thes e results suggest that the major mode of action of EGFr/TGF alpha in n ormal and benign prostate is that of a paracrine or juxtacrine loop, t he ligand being expressed in the stroma cells and the receptor in the epithelial cells. Since a subset of prostatic carcinomas coexpressed t he ligand and the receptor in their tumor cells, it is suggested that an independent autocrine signaling mechanism may occur and grant a sel ective advantage for the growth of prostate cancers.