Expression of the IIIc Variant of FGF Receptor-1 Confers Mitogenic Responsiveness to Heparin and FGF-5 in TAKA-1 Pancreatic Ductal Cells.

Human pancreatic cancer is a devastating diseasewith a poor prognosis (1). Although the exact reasonsfor the aggressive nature of this disorder are unknown, certain observations have pointed to theimportant role of growth factors in its pathobiology(2). Many of these cancers frequently overexpressfibroblast growth factors (FGFs) (3). FGF signalingis mediated through four high-affinity tyrosine kinasereceptors, termed fibroblast growth-factor receptors(FGFRs) (3,4). The extracellular domain of FGFRsis usually composed of three immunoglobulin (Ig)-like domains (I-III), a transmembrane region followedby a juxtamembrane domain, and a splittyrosine kinase catalytic domain. Several isoformsof FGFR-1, -2, and -3 have been identified, some of which exhibit different ligand-binding properties(3,5). Alternative splicing of the second half of Igdomain III of FGFR-1 results in three receptor variants,termed IIIa, IIIb, and IIIc. The IIIa splice variantyields a secreted receptor that is devoid of anysignaling capacity (5). The expression of the IIIbvariant is generally restricted to epithelial cell types,whereas the expression of the IIIc variant is restrictedto mesenchymal cell types (6-11).