EXPRESSION OF A BINDING-PROTEIN FOR FGF IS ASSOCIATED WITH EPITHELIALDEVELOPMENT AND SKIN CARCINOGENESIS

Fibroblast growth factors (FGF)-1 and -2 are found in most embryonic a nd adult normal and tumor tissues, where they are immobilized in the e xtracellular matrix (EM), Mobilization of these FGFs is part of a tigh tly controlled process resulting in the activation of high-affinity re ceptors, Recently, we have shown that a novel human FGF-binding protei n (FGF-BP) mediates the release of immobilized FGF-2 from the EM. Here we isolated genomic and cDNA clones of the mouse FGF-BP homologue and studied its expression during embryonic development and skin carcinog enesis, The murine gene contains two exons that generate a 1.2 kb mRNA and predicts an 18 kDa secreted protein that is 63% identical to its human homologue, FGF-BP mRNA expression during embryogenesis is restri cted to skin, intestine and lung. In the developing skin, FGF-BP expre ssion starts at embryonic day 9, reaches peak levels perinatally and i s downregulated during postnatal development. Develepment regulation i n the intestine is similar, but in lungs and ovaries high expression w as also observed in the adult, FGF-BP mRNA expression in the adult ski n is dramatically increased during early stages of carcinogen-induced transformation in vivo and by rasactivation in vitro, Finally, mouse F GF-BP binds to FGF-2 and can function as a modulator of FGF in FGF-res ponsive cells, Our results suggest a potential function of FGF-BP duri ng development and tumorigenesis.