Fibroblast Growth Factor Receptor 4, Implicated in Progression of Islet Cell Carcinogenesis by Its Expression Profile, Does Not Contribute Functionally'

Fibroblast growth factor receptor 4 (FGFR4) gene expression is activated in late-stage �-ceII tumors that develop in transgenic mice harboring SV4O large T antigen (Tag) gene that is under the transcriptional control of the insulin promoter (RIP-Tag). The FGFR4 gene was active in cell lines derived from tumors but not in cells derived from hyperplastic islets. We used both gain-of-function and loss-of-function FGFR4 transgenic mice to determine whether FGFR4 modulates islet cell tumongenesis and, if so, to identify the nature of the effect. Both types of FGFR4 transgenic mice were viable and fertile and developed islet tumors when crossed with RIP-Tag mice. Remarkably, there was no significant perturbation in the tumorigenesis pathway resulting from either chronic up-regulation or absence of FGFR4 gene expression. Analyses included the incidence and size of tumors, rate of cell proliferation, cell density, and life span. We conclude that FGFR4 gene activation is a marker of but is not causal for fl-cell transformation.