Gene regulation and cell differentiation of FGF8

1.Fgf8基因调控特性Fgf8基因的启动子在300b.p。位于5‘侧翼的区域。在10 nM睾酮存在下，其启动子活性不受影响。此外，各种报告结构，包括内含子和3‘-区，在Fgf8基因中没有显示任何雄激素反应区域。雄激素非依赖性志诺木癌细胞分泌生长因子的分离：由于激活素结合蛋白-卵泡抑素完全阻断了刺激生长的事实，并且在部分纯化的组分中发现了具有抗激活素βA和βB抗体的免疫活性物质，因此该分泌的生长因子最终被鉴定为激活素。激活素在雄激素不敏感的人前列腺癌PC-3细胞中也有明显的表达，但在雄激素敏感的LNCaP细胞中很少表达，这表明激活素的表达与激素不敏感的生长条件有关。FGF8在人类肿瘤和小鼠胚胎中的表达：利用我们新建立的抗小鼠和人FGF8的中和性单抗，用免疫组织化学方法检测了不同标本中FGF8的表达。在人类癌症标本中，FGF8在前列腺癌中频繁表达，但在前列腺增生症中不表达。在小鼠胚胎中，FGF8在分化的神经细胞中有较强的表达。此外，FGF8还能促进培养的大鼠嗜铬细胞瘤PC12细胞突起的生长。

1. Characterization of fgf8 gene regulation The promoter of the fgf8 gene was found within 300 b.p. of the 5'-flanking region. Its promoter activity was not affected in the presence of 10 nM testosterone. In addition, various reporter constructs, including the introns and the 3'-region, failed to show any androgen-responsive region in the fgf8 gene.2. Isolation of a growth factor secreted from androgen-independent Shionogi carcinoma cells: The secreted growth factor was finally identified as activin from the facts that the stimulated growth is completely blocked by activin-binding protein, follistatin, and that immunoreactive substances with anti-activin βA and βB antibodies are found in the partially purified fractions. Activin expression was also marked in androgen-insensitive human prostate cancer PC-3 cells, but, scarce in androgen-sensitive LNCaP cells, suggesting that activin expression is correlated with hormone-unresponsive growth condition.3. FGF8 expression in human cancers and murine embryos: By use of our newly established neutralizing monoclonal antibody against murine and human FGF8, expression of FGF8 in various specimens was immunohistochemically examined. In human cancer specimens, FGF8 was frequently expressed in prostate cancers, but, not in prostate hyperplasias. In murine embryos, FGF8 was strongly expressed in differentiated neuronal cells. In addition, FGF8 had ability to promote neurite extension in cultured rat pheochromacytoma PC12 cells.