Fig. 4. PLK4 overexpression can delay DNA damage–induced malignancies.

(A) Plk4 mRNA expression normalized to Hprt levels in thymus and total bone marrow isolated from rtTA (n = 7) and rtTA/Plk4 (n = 7) transgenic mice fed with doxycycline-containing diet for 5 days. (B) Percentage of thymocytes or LSK cells presenting with 2, 3, 4, or >4 centrioles. Cells were isolated from rtTA (n = 2) and rtTA/Plk4 (n = 2) transgenic mice fed with doxycycline-containing diet for 5 days. A minimum of 160 cells were counted per condition. (C) Kaplan-Meier analysis of tumor-free survival of mice kept on doxycycline during the weekly cycles of IR (4 × 1.75 Gy). rtTA, median survival 125 days (n = 11); rtTA/Plk4, median survival 164 days (n = 12). Log-rank (Mantel-Cox) P = 0.0159 (χ² = 5.817), Breslow-Gehan-Wilcoxon P = 0.0099 (χ² = 6.658). (D) Plk4 mRNA expression in tumor cell lines established from diseased rtTA (n = 3) and rtTA/Plk4 transgenic mice (n = 3) shown in (C), treated with doxycycline for 48 hours. (E) Kaplan-Meier analysis of tumor-free survival of rtTA (n = 9) and rtTA/Plk4 (n = 12) transgenic mice injected with either 3-MC or vehicle. All animals were kept continuously on doxycycline-containing food. Median latency 92 versus 105.5 days. Log-rank (Mantel-Cox) P = 0.0130 (χ² = 6.176), Breslow-Gehan-Wilcoxon P = 0.0205 (χ² = 5.372). Tukey’s multiple comparisons test was used to compare Plk4 mRNA data. Centriole quantifications data were tested by Sidak’s multiple comparisons test. *P < 0.05, **P < 0.01, ***P < 0.005.