Meta-Biol

• Pathways

Overexpression of WT FGFR3 is weakly transforming when expressed in a mouse haematopoietic model, while expression of translocated FGFR3 carrying activating point mutations in the coding sequence is strongly transforming in both NIH 3T3 cells and the haematopoietic mouse model (Chesi, 2001; Ronchetti, 2001; Li, 2001). Activating mutations in FGFR3 are mutually exclusive with activating Ras mutations, and focus formation in NIH 3T3 cells is inhibited by cotransfection with dominant negative forms of ras or raf, suggesting that activation of the MAPK pathway is the primary oncogenic event in translocated myeloma lines (Chesi, 2001). Inhibition of FGFR3 in multiple myeloma lines and tumors has been shown to inhibit proliferation (Grand, 2004; Qing, 2009; Trudel, 2009; Krejci, 2010)