Mutant fibroblast growth factor receptor 3 induces intracellular signaling and cellular transformation in a cell type- and mutation-specific manner

摘要: Although activating mutations of fibroblast growth factor receptor 3 (FGFR3) are frequent in bladder tumors, little information is available on their specific effects urothelial cells or the basis for observed mutation spectrum. We investigated phenotypic and signaling consequences three FGFR3 (S249C, Y375C, K652E) immortalized normal human (TERT-NHUC) mouse fibroblasts (NIH-3T3). In TERT-NHUC, all mutant forms induced phosphorylation FRS2α ERK1/2, but not AKT SRC. PLCγ1 was only TERT-NHUC expressing common S249C Y375C mutations, rare K652E mutation. Cells displayed an increased saturation density, related to proliferation viability. This effect significantly dependent undetectable FGFR3, which failed phosphorylate PLCγ1. contrast expression NIH-3T3 resulted Src Akt. addition, were able Plcγ1 induce morphological transformation, cell proliferation, anchorage-independent growth. Our results indicate that both type specific. Mutant may confer a selective advantage urothelium by overcoming contact inhibition proliferation.