Gene regulation and cell differentiation of FGF8

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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.