Fig. 4.

Inhibition of FGFR-TK activity corrects the aneuploidy and suppresses tumor growth initiated by FGFR3-TACC3. (A) Karyotype analysis of Rat1A cells transduced with control or FGFR3-TACC3 lentivirus and treated with vehicle [dimethyl sulfoxide (DMSO)] or PD173470 (100 nM) for 5 days. (B) Correction of premature sister chromatid separation (PMSCS) by PD173470 in cells expressing FGFR3-TACC3. Panels show representative metaphase spreads. (C) Quantitative analysis of metaphases with loss of sister chromatid cohesion (FGFR3-TACC3 treated with DMSO versus FGFR3-TACC3 treated with PD173470). P = 0.001; error bars indicate SD. (D and E) Growth-inhibition assays of Rat1A cells transduced with the indicated lentivirus (D) and GSC-1123 (E) treated with PD173470 at the indicated concentrations. Cells were treated for 3 days (D) or for the indicated time (E). Cell viability was determined by the MTT assay. Error bars show means ± SE (n = 4 culture wells). AU, arbitrary units. (F) Survival of glioma-bearing mice was tracked after intracranial implantation of Ink4A;Arf−/− astrocytes transduced with FGFR3-TACC3. After tumor engraftment, mice were treated with vehicle or AZD4547 (50 mg/kg) for 20 days (vehicle, n = 7 animals; AZD4547, n = 6; P = 0.001).