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. Author manuscript; available in PMC: 2019 Aug 15.
Published in final edited form as: Cancer Res. 2018 May 14;78(16):4642–4657. doi: 10.1158/0008-5472.CAN-17-1925

Figure 2. Adaptive responses to tipifarnib in Hras-mutant thyroid cancers.

Figure 2

A. Tumor bearing Hras;p53 mice were treated with vehicle (n=9) or 80 mg/kg BID tipifarnib (n=6) for 14 days. Thyroid volume was calculated using 3D ultrasound. B. Reduction in pERK and pMEK in Hras;p53 tumor lysates from mice treated with tipifarnib for 72h. Black arrow: farnesylated Hras; red arrow: defarnesylated Hras. C,D. Western blots of human HRAS-mutant thyroid cancer cell lines exposed to increasing concentrations of tipifarnib for 72h. Wild-type RAS-GTP levels increase with greater concentrations of tipifarnib. Arrows show molecular weight shift with HRAS defarnesylation. E,F. Western blot showing a reduction of pERK in tipifarnib-treated C643 and HTH83 cells collected at 72h with knockdown of both wild-type RAS proteins. G. Effect of exposure to individual ligands for 72h on the growth response to 100 nM tipifarnib in Hth83 cells (performed in triplicate). Growth in tipifarnib-treated cells exposed to FGF2, EREG, HGF, FGF6, and EGF was greater than in the absence of ligand (*p<0.05, t-test). H. Effects of ligand exposure on response to tipifarnib in C643 cells (performed in triplicate). Growth in the presence of 100nM tipifarnib was greater after exposure to EGF, EFNB2, EFNB3, HGF, FGF6, PDGF, FGF2 compared to no ligand (*p<0.05, t-test).