Figure 6.

Nuclear localization of BRAF^V600E promotes vemurafenib resistance and tumor growth in thyroid cancer mouse model. (A, B) ERK1/2 activity was assessed by its phosphorylation in stably transfected BRAF^V600E or NLS-BRAF^V600E cells after treating KAT18 (A) and TPC-1 (B) cells with 5 µM PLX-4032 or DMSO at different time points. (C) KAT18 cells transduced with lentiviral vectors carrying NLS-BRAF^V600E, BRAF^V600E or NLS followed by vemurafenib treatment for 24 h and then fixed and stained with PI to evaluate the effect of nuclear BRAF^V600E on cell cycle using flowcytometric analysis. (D) Female nude mice (five mice per group) were orthotopically injected in thyroid gland with TPC-1 cells transduced with either NLS-BRAF^V600E or BRAF^V600E (1×10⁶ cells/mouse). Tumor size was monitored twice a week for 6 weeks during vemurafenib treatment (50 mg/kg/day). * indicates significance at P<0.010.