Fig. 7. Tumor growth is reduced by Notch1 inactivation.
a, Highly induced YFPCreNotch1+/flox (+/−) and YFPCreNotch1flox/flox (−/−) mice or uninduced control (+/+) mice were treated with DEN and SOR and aged for 28 weeks. For b–d, Notch1+/+, n = 11; Notch1+/− n = 10; Notch1−/−, n = 12. b, Representative images of esophagi for each genotype. Scale bar, 1 mm. c, Tumor density per genotype. Mean ± s.e.m., each dot represents a mouse. One-way ANOVA; adjusted P values from Tukey’s multiple comparisons test. d, Tumor areas per genotype. Mean± s.e.m., each dot represents a tumor. Kruskal–Wallis test; adjusted P values from Dunn’s multiple comparisons test. e,f, Tumors from Notch1+/+ (e) and Notch1−/− (f) epithelium were sectioned and stained for H&E (left panel), for keratinocyte progenitor marker Keratin 14 (KRT14, green), and NOTCH1 (magenta) (middle panel) or keratinocyte differentiation marker Loricrin (LOR, magenta) and progenitor markers ITGA6 (gray) and KRT14 (green) (right panel). DNA is blue. Images representative of n = 19 tumors from Notch1+/+ and n = 13 tumors from Notch1−/− epithelium. Scale bars, 250 µm. g, Uninduced YFPCreNotch1flox/flox mice (+/+) were treated with DEN/SOR and aged for 9 weeks. Mice were treated with anti-NOTCH1 NRR1.1E3 or with CTRL for 6 weeks before collection. h, Representative tumors marked by KRT6a staining (red) are shown with white arrowheads in esophageal epithelium from control and anti-NRR1.1E3 treated mice. Scale bars: 100 µm. i, Quantification of tumor area (mean ± s.e.m., each dot represents a tumor, n = 4 mice per group). P values from two-tailed Mann–Whitney test. Data are shown in Supplementary Table 24.