Supplementary Figure 10: Erlotinib treatment activates Axl–JNK–ERK signaling in orthotopic models; this is suppressed by TNF inhibition.
From: A TNF–JNK–Axl–ERK signaling axis mediates primary resistance to EGFR inhibition in glioblastoma
(a) Immunostainig of pAXL, pJNK and pERK proteins from a representative brain section from vehicle, erlotinb and erlotinib plus thalidomide group. Cells with brown staining are considered as positive. Erlotinib group shows higher expression of pAxl, pJNK and pERK compared to vehicle group, whereas thaldimide inhibits erlotinib induced pAxl-pJNK-pERK activation. (b-d) Semi-quantitative analysis of pAxl, pJNK and pERK immunostaining. Four random fields in 3 tissue blocks at x200 magnification were scored semiquantitatively as: 0=No positive staining; 1=1-25% tumor cells stained, 2=26%-75% tumor cells stained and 3=>75% tumor cells stained. Differences between treatment groups were analyzed by the Mann-Whitney U test (n=12). (b) pAXL: Erlotinib vs. vehicle, p=0.0062, U=26; Erlotinib vs. erlotinib+thalidomide, p=0.0093, U=28. (c) pJNK: Erlotinib vs. vehicle, p=0.022, U=32; Erlotinib vs. erlotinib+thalidomide, p=0.014, U=29.5. (d) pERK: Erlotinib vs. vehicle, p=0.0040, U=23.5; Erlotinib vs. erlotinib+thalidomide, p=0.0026, U=21.
