Recombinant Human FGF-8e Protein, CF

FGF-8 is a member of the fibroblast growth factor family that was originally discovered as a growth factor essential for the androgen-dependent growth of mouse mammary carcinoma cells (1 - 4). Alternate splicing of mouse FGF-8 mRNA generates eight secreted isoforms, designated a - h. Only FGF-8a, b, e and f exist in humans (4). FGF-8 contains a 22 amino acid (aa) signal sequence, an N-terminal domain that varies according to the isoform (84 aa for FGF-8e; 20 aa for the shortest, FGF-8a), a 125 aa FGF domain and a 37 aa proline-rich C-terminal sequence. The FGF domain of FGF-8 shares the most aa identity with FGF17 (75%) and FGF-18 (67%), and the three form an FGF subfamily (2). Human FGF-8e shares 98%, 99% and 93% aa identity with mouse, rat and canine FGF-8e. FGF-8 is widely expressed during embryogenesis, and mediates epithelial-mesenchymal transitions. It plays an organizing and inducing role during gastrulation, and regulates patterning of the midbrain/hindbrain, eye, ear, limbs and heart in the embryo (2, 5 - 8). The isoforms may play different roles in development. For example, FGF-8a expands the midbrain in transgenic mice, while FGF-8b transforms midbrain into cerebellum (5). FGF-8 activates the ‘c’ splice forms of fibroblast growth factor receptors FGF R2, FGF R3, and FGF R4, with differential activity among the FGF-8 isoforms (2, 9). FGF-8b shows the strongest receptor affinity and oncogenic transforming capacity, although FGF-8a and e are also transforming and have been found in human prostate, breast or ovarian tumors (1, 5, 10 - 13). FGF-8 shows limited expression in the normal adult, but low levels are found in the reproductive and genitourinary tract, peripheral leukocytes and bone marrow hematopoietic cells (3, 10, 14).