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 8.
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.
Tanaka
A
A
Department of Pathology, Jichi Medical School, Kawachi, Tochigi, Japan. atanaka@jichi.ac.jp
Furuya
A
A
Yamasaki
M
M
Hanai
N
N
Kuriki
K
K
Kamiakito
T
T
Kobayashi
Y
Y
Yoshida
H
H
Koike
M
M
Fukayama
M
M
D000818:Animals; D000911:Antibodies, Monoclonal; D001940:Breast / Q000737:chemistry* / Q000473:pathology; D001943:Breast Neoplasms / Q000737:chemistry; D005260:Female; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors; D006133:Growth Substances / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D009363:Neoplasm Proteins / Q000032:analysis*; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000473:pathology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; C496456:FGF8 protein, human; C496457:Fgf8 protein, mouse; D006133:Growth Substances; D009363:Neoplasm Proteins; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors