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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 against FGF 8¹

Departments of Pathology [A. T., K. K., T. K., M. F.] and Urology [Y. K.], Jichi Medical School, Minamikawachi, Kawachi, Tochigi 329-0498; Kyowa Hakko Kogyo Tokyo Research Laboratories, Machida, Tokyo 194-8533 [A. F., M. Y., N. H.]; Department of Pathology, Faculty of Medicine, Kogoshima University, Kogoshima 890-0075 [H. Y.]; and Department of Pathology, Tokyo Metropolitan Komagome Hospital, Bunkyo, Tokyo 113-0021 [M. K.], Japan

Fibroblast growth factor (FGF) 8, also known as androgen-induced growth factor, was originally isolated from an androgen-dependent mouse mammary Shionogi carcinoma SC-3 cell line, in which it was shown to have androgen-regulated properties. We previously demonstrated that Fgf 8 transcripts were detected in several human prostate and breast cancer cell lines and that recombinant FGF 8 was mitogenic to an androgen-sensitive prostate cancer LNCaP cell line. In this study, to characterize the roles of FGF 8 in clinical hormone-responsive cancers, we established a monoclonal antibody against FGF 8. In Western blots, this antibody specifically interacted with a FGF 8b isoform that was identical between 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 established anti-FGF 8 antibody blocked androgen- and FGF 8-stimulated growth but not basic FGF-stimulated growth. Immunohistochemical analyses by use of the established anti-FGF 8 antibody demonstrated that FGF 8 was frequently expressed in human prostate cancers, appearing in 40 of 43 cases (93%), whereas both prostatic hyperplasia specimens and normal prostate tissues included in biopsy specimens were negative for FGF 8 expression. On the other hand, FGF 8 was detected in normal ductal and lobular epithelial cells in breast tissues. FGF 8 was also frequently expressed in various breast diseases, including fibroadenomas (5 of 5 cases, 100%), intraductal papillomas (3 of 3 cases, 100%), ductal hyperplasias (3 of 6 cases, 50%), and breast cancers (8 of 12 cases, 67%). Androgen receptors were also immunohistochemically detected in FGF 8-positive prostate cancers (40 of 40 cases, 100%) and FGF 8-positive breast diseases (17 of 19 cases, 89%). These findings strongly suggest that FGF 8 is involved in hormone-related tumorigenesis of the prostate and breast.

¹ Supported in part by a Grant-in-Aid for Scientific Research from the Japanese Ministry of Education, Science, Sports and Culture.

² To whom requests for reprints should be addressed, at Department of Pathology, Jichi Medical School, 3311-1 Yakushiji, Minamikawachi, Kawachi, Tochigi 329-0498, Japan. Phone: 81 285-44-2111; Fax: 81 285-44-8467; E-mail: atanaka@jichi.ac.jp.

Received 2/20/98. Accepted 3/31/98.

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