(A–C) Relative survival for SMB21 cells expressing candidate genes treated with LDE225 (72 hrs). HRAS(G12V), BRAF(V600E), not PIK3CA(H1047R) or myristoylated AKT, confer resistance. (mean ± s.e.m., n > 5).
(A’) Elevated phospho-Erk in SMB21 cells expressing HRAS(G12V) or BRAF(V600E).
(B’–C’) Elevated phospho-AKT in SMB21 cells expressing PIK3CA(H1047R) or AKT(Myr).
(D) SMB21(HRAS) cells initiate resistant tumors in vivo. Tumor volume over time. Mean ± s.e.m., n = 5. (Experiments were performed concurrently with Fig. 2C, the same SMB21 control shown here and Fig 2C.)
(E) Phospho-Erk in sensitive and resistant tumors from engrafted SMB21 cells mean ± s.e.m, * p < 0.05, unpaired student t-test.