Fig. 6: Downregulation of human TYMS (hTS) increases survival of hTS/Ink4a/Arf −/− GEMM.
From: TYMS promotes genomic instability and tumor progression in Ink4a/Arf null background
A Experimental design showing timeline to study the effect of TS downregulation in vivo. hTS/Ink4a/Arf −/− mice were injected with one dose of lentiviral TS shRNA#61 and TS shRNA #64 or non-specific (NS) shRNA control at 2 months of age and sacrificed when showed signs of sickness at the end of life. B Kaplan-Meier survival graph of hTS/Ink4a/Arf −/− mice after one IP injection of TS shRNA#61 (n = 16) and TS shRNA#64 (n = 11) compared to control non-specific shRNA (NS, n = 14). Median survival for animals injected with TS shRNA#61 was 211.5 days (95% CI, 176–286 days,) for shRNA#64 group was 222 days (95% CI, 174–282 days) and for NS shRNA group was 171 days (95% CI, 155–219). *P = 0.0430 and *P = 0.0295, respectively calculated by log-rank Mantel-Cox test. C Percent of live and deceased animals treated with TS shRNA#61 and #64 compared to NS shRNA at 171 days. This time point corresponds to the median survival for NS shRNA control group. D Splenic tumors derived from hTS/Ink4a/Arf −/− treated with TS shRNA #61 and #64 compared to control NS shRNA immunoblotted for TS and γH2AX (Ser139). Three representative tumors per group are shown. GAPDH is used as loading control.
