Fig. 1. Missense and null Trp53 mutations promote mouse colon tumor progression in CDX2P-CreER^T2 Apc ^fl/+, Kras ^LSL-G12D (AK) mice.

a Kaplan-Meier survival curves of CDX2P-CreER^T2AK (AK) mice (n=10, median survival = 336 days), CDX2P-CreER^T2AKP^270/+ (AKP^270/+) mice (n=16, median survival = 166 days), CDX2P-CreER^T2AKP^fl/fl (AKP^fl/fl) mice (n=16, median survival = 97 days) and CDX2P-CreER^T2AKP^270/fl (AKP^270/fl) mice (n=20, median survival = 88 days). TAM was administered daily for two days and time zero represents the second of these days. P-values were obtained by log-rank test in the following comparisons: P = 1.4E-6 for AK vs. AKP^270/+; P = 1.4E-7 for AKP^fl/fl vs. AKP^270/+; P = 1.9E-8 for AKP^270/fl vs. AKP^270/+. b Percent of colon tumors with different depths of invasion from AK mice, AKP^270/+ mice, AKP^fl/fl mice and AKP^270/fl mice. Data are from multiple lesions per mouse (n=10–14 mice per group). P-values based on Fisher Exact tests and Exact Poisson tests are shown in Table 1 and Supplementary Table 1, respectively. Error bars are standard error of the mean. A: adenoma; SM: submucosa; MP: muscularis propria; SS: subserosa; S: serosa. c, d Hematoxylin and eosin (H&E) staining of representative invasive tumors from proximal colon (right) and cecum (left) tissues are shown for AKP^270/fl mice (c) and AKP^fl/fl mice (d). Tumors in (c) and (d) were collected 3 months after TAM injection. Images with high magnification are shown in the bottom panels and are boxed in the lower magnified areas in the corresponding top panels. The dashed lines indicate the boundary between muscular layer and subserosa. Scale bars: 500 μm for low magnification image (top panels); 100 μm for high magnification images (bottom panels).