RAP inhibits polyp formation and progression in a mouse model of colon polyposis.

(A–C) CDX2P-CreER^T2 Apc^fl/fl mice were administered TAM to induce Apc mutation-dependent polyposis and were then monitored by video-endoscopy for polyp formation after treatment with vehicle (circle) or RAP (triangle). Scores of polyp severity in RAP- and vehicle-treated mice groups were determined at 2, 6, and 12 weeks for all mice that were alive. Each circle or triangle represents an individual mouse (N = 6 per group). The numbers of mice requiring euthanasia due to illness are represented at the top of each graph. The polyp scores were statistically lower by 12 weeks of treatment using 2-sample Z-tests of the proportions of mice with score 4 or higher (N = 6 per group, at 2 weeks, p = 0.12; at 6 weeks, p = 0.08; at 12 weeks, p = 0.01, * signifies p = 0.01). (D) Representative endoscopic pictures of the mouse colons from a control wild-type mouse and TAM-treated and TAM- plus RAP-treated CDX2P-CreER^T2 Apc^fl/fl mice, with inhibition of polyposis by RAP treatment in the model. Polyps are indicated by black arrows.