Figure 4: Bcl-2 loss impairs adenoma formation.

(a) Representative hematoxylin and eosin (H&E) stained sections of two small intestines of the Lgr5.Bcl-2^+/+.Apc^fl/fl and Lgr5.Bcl-2^fl/fl.Apc^fl/fl mice at day 30 post induction. Arrows indicate an adenomatous lesion. Scale bars, 2 mm. (b) Graph showing the number of adenomas at day 30 post induction for Lgr5.Bcl-2^+/+.Apc^fl/fl, Lgr5.Bcl-2^+/fl.Apc^fl/fl and Lgr5.Bcl-2^fl/fl.Apc^fl/fl mice. Each dot represents a mouse (n=5), error bars represent s.e.m. **P<0.01, ****P<0.0001, Student’s t-test. (c) Graph showing the adenoma size at day 30 post induction in Lgr5.Bcl-2^+/+.Apc^fl/fl, Lgr5.Bcl-2^+/fl.Apc^fl/fl and Lgr5.Bcl-2^fl/fl.Apc^fl/fl mice. Each dot represents a measurement of the adenoma size (minimal n=32 per genotype), error bars represent the s.e.m. **P<0.01, ***P<0.001, Student’s t-test. (d) Kaplan–Meier plot demonstrating the surviving fraction at the indicated time points post induction of Lgr5.Bcl-2^+/+.Apc^fl/fl, Lgr5.Bcl-2^+/fl.Apc^fl/fl and Lgr5.Bcl-2^fl/fl.Apc^fl/fl mice (minimal n=10 mice per genotype). P value by log-rank test. (e) Graph indicating the number of adenomas per mice at the time of culling in the survival analysis (n=4). Error bars represent the s.e.m., ***P<0.001, ****P<0.0001, Student’s t-test. (f) Representative images of distal part of the small intestines of Lgr5.Bcl-2^+/+.Apc^fl/fl and Lgr5.Bcl-2^fl/fl.Apc^fl/fl mice, included in the survival analysis, at the time of termination. (g) Representative immunohistochemical panel of Apc-deficient adenomas (top panel) and cyst-like structures (bottom panel) in the small intestines of mice of the indicated genotypes 30 days after induction; H&E (left), Lgr5-GFP (middle-left), β-catenin (middle-right) and BCL-2 (right) staining. Scale bars, 50 μm. The graph displays the fraction of cyst-like structures observed in mice of the indicated genotypes at moment of termination. Each dot represents a mouse (n=3), error bars represent the s.e.m. ****P<0.0001, Student’s t-test.