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 polypeptides implicated in a number of physiological and pathological processes. They bind to at least three types of cell surface molecules, including low and high affinity receptor families. The role of FGFs and their receptors in human tumorigenesis has been suspected but not formally proven. FGF6 is an oncogene encoding a precursor protein of 208 amino acids that has been shown to bind to FGF receptors. Its normal function has not been identified, but its restricted pattern of expression suggests a role in muscle development or function. We have constructed, produced, and purified a diphtheria toxin/FGF6 mitotoxin that selectively 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 transduction pathway that does not involve FGF receptor.
Laboratoire d'Oncologie Moléculaire, Unité 119 de I'INSERM, Marseille, France.
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D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004167:Diphtheria Toxin / Q000494:pharmacology*; D051522:Fibroblast Growth Factor 6; D005346:Fibroblast Growth Factors; D005822:Genetic Vectors; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008934:Mitogens / Q000494:pharmacology*; D016716:PC12 Cells; D011518:Proto-Oncogene Proteins / Q000494:pharmacology*; D051381:Rats; D017468:Receptors, Fibroblast Growth Factor / Q000032:analysis*
D004167:Diphtheria Toxin; C496452:FGF6 protein, human; C486115:Fgf6 protein, mouse; C486116:Fgf6 protein, rat; D051522:Fibroblast Growth Factor 6; D008934:Mitogens; D011518:Proto-Oncogene Proteins; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors; D006493:Heparin