Fig. 3

TAS-120 reversed FGF2 induced paradoxical growth effects in FGFR1 amplified and non-amplified ER + BC cells. (A) Spheroid images of FGFR1 amplified cells (CAMA1 and MDA-MB-134) and non-amplified cells (MCF7 and T47D) are shown after incubation with different doses (0.2 and 1.0µM) of TAS-120 and FGF2 (25 ng/mL) for 14 days. Bar equals 1000 μm. (B) Relative fold change of ratio between cell number in + FGF2 vs. -FGF2 spheroids in Panel A are depicted, with the DMSO control group serving as controls and set to a fold of one. C-D. Relative mRNA expression level of FGFR1 (C) and ratio of p21/CCND1 (D) in ER + cell 3D cultures incubated with different doses (0.2 and 1.0 µM) of TAS-120 plus FGF2 (25 ng/mL) for 72 h. The mRNA expression was normalized to RPLP0 and the control treatments, using DMSO, are set to a fold of one. E. Plots that depict the relationship between the expression levels of FGF2 (X-axis) and the CDKN1A/CCND1 ratio (Y-axis) in 601 ER + breast cancer patients from TCGA. The three linear fit curves and 95% C.I. (grey shaded area) demonstrate the interaction effects between FGF2 and FGFR1 expression, where FGFR1 expression levels are grouped into tertiles (high n = 206; low n = 199; med n = 196)