Tanaka A, Furuya A, Yamasaki M, Hanai N, Kuriki K, Kamiakito T, Kobayashi Y, Yoshida H, Koike M, Fukayama M
Department of Pathology, Jichi Medical School, Kawachi, Tochigi, Japan.
Cancer Res. 1998 May 15;58(10):2053-6.
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.
成纤维细胞生长因子（FGF）8，也被称为雄激素诱导生长因子，最初是从雄激素依赖性小鼠乳腺腺癌Shionogi癌SC-3细胞系中分离出来的，在该细胞系中它显示出具有雄激素调节特性。我们之前证明，在几种人前列腺和乳腺癌细胞系中检测到了Fgf 8转录本，并且重组FGF 8对雄激素敏感的前列腺癌LNCaP细胞系具有促有丝分裂作用。在本研究中，为了确定FGF 8在临床激素反应性癌症中的作用，我们制备了一种针对FGF 8的单克隆抗体。在蛋白质免疫印迹分析中，该抗体与FGF 8b亚型特异性相互作用，FGF 8b亚型在小鼠和人类之间是相同的，但与其他鼠类8a和8c亚型不同。在使用SC-3细胞的细胞生长试验中，新制备的抗FGF 8抗体阻断了雄激素和FGF 8刺激的生长，但未阻断碱性FGF刺激的生长。使用制备的抗FGF 8抗体进行免疫组织化学分析表明，FGF 8在人前列腺癌中经常表达，在43例中有40例（93%）出现，而活检标本中的前列腺增生标本和正常前列腺组织FGF 8表达均为阴性。另一方面，在乳腺组织的正常导管和小叶上皮细胞中检测到FGF 8。FGF 8在各种乳腺疾病中也经常表达，包括纤维腺瘤（5例中的5例，100%）、导管内乳头状瘤（3例中的3例，100%）、导管增生（6例中的3例，50%）和乳腺癌（12例中的8例，67%）。在FGF 8阳性的前列腺癌（40例中的40例，100%）和FGF 8阳性的乳腺疾病（19例中的17例，89%）中也通过免疫组织化学检测到了雄激素受体。这些发现强烈表明FGF 8参与了前列腺和乳腺的激素相关肿瘤发生。
