HIGH-FREQUENCY OF FIBROBLAST-GROWTH-FACTOR (FGF)-8 EXPRESSION IN CLINICAL PROSTATE CANCERS AND BREAST TISSUES, IMMUNOHISTOCHEMICALLY DEMONSTRATED BY A NEWLY ESTABLISHED NEUTRALIZING MONOCLONAL-ANTIBODY AGAINSTFGF-8

Fibroblast growth factor (FGF) 8, also known as androgen-induced growt h factor, was originally isolated from an androgen-dependent mouse mam mary Shionogi carcinoma SC-3 cell line, in which it was shown to have androgen-regulated properties. We previously demonstrated that Fgf 8 t ranscripts were detected in several human prostate and breast cancer c ell lines and that recombinant FGF 8 was mitogenic to an androgen-sens itive prostate cancer LNCaP cell line. In this study, to characterize the roles of FGF 8 in clinical hormone-responsive cancers, we establis hed a monoclonal antibody against FGF 8, In Western blots, this antibo dy specifically interacted with a FGF 8b isoform that was identical be tween mouse and human but was not identical to other murine 8a and 8c isoforms, In a cell growth assay using SC-3 cells, the newly establish ed anti-FGF 8 antibody blocked androgen-and FGF 8-stimulated growth bu t not basic FGF-stimulated growth. Immunohistochemical analyses by use of the established anti-FGF 8 antibody demonstrated that FGF 8 was fr equently expressed in human prostate cancers, appearing in 40 of 43 ca ses (93%), whereas both prostatic hyperplasia specimens and normal pro state tissues included in biopsy specimens were negative for FGF 8 exp ression. On the other hand, FGF 8 was detected in normal ductal and lo bular epithelial cells in breast tissues. FGF 8 was also frequently ex pressed in various breast diseases, including fibroadenomas (5 of 5 ca ses, 100%), intraductal papillomas (3 of 3 cases, 100%), ductal hyperp lasias (3 of 6 cases, 50%), and breast cancers (8 of 12 cases, 67%). A ndrogen receptors were also immunohistochemically detected in FGF I-po sitive prostate cancers (40 of 40 cases, 100%) and FGF 8-positive brea st diseases (17 of 19 cases, 89%), These findings strongly suggest tha t FGF 8 is involved in hormone-related tumorigenesis of the prostate a nd breast.