A DIPHTHERIA-TOXIN FIBROBLAST GROWTH-FACTOR-6 MITOTOXIN SELECTIVELY KILLS FIBROBLAST GROWTH-FACTOR RECEPTOR-EXPRESSING CELL-LINES

The fibroblast growth factors (FGFs) constitute a family of nine polyp eptides implicated in a number of physiological and pathological proce sses. They bind to at least three types of cell surface molecules, inc luding low and high affinity receptor families The role of FGFs and th eir receptors in human tumorigenesis has been suspected but not formal ly proven. FGF6 is an oncogene encoding a precursor protein of 208 ami no acids that has been shown to bind to FGF receptors. Its normal func tion has not been identified bit its restricted pattern of expression suggests a role in muscle development or function. We nave constructed , produced, and purified a diphtheria toxin/FGF6 mitotoxin that select ively kills FGF receptor-expressing cells. Interestingly, at least two cell lines that normally respond to FGF6 have been found resistant to DT/FGF6, suggesting that FGF6 acts on these cells through a transduct ion pathway that does not involve FGF receptor.