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. Author manuscript; available in PMC: 2020 Mar 1.
Published in final edited form as: Cancer Res. 2019 Jan 24;79(5):954–969. doi: 10.1158/0008-5472.CAN-18-1790

Figure 2.

Figure 2.

PPARD accelerates APC mutation-driven intestinal tumorigenesis in mice. A and B, Effects of PPARD overexpression on intestinal tumorigenesis in Apcmin mice. A, Representative images of H&E-stained intestines of Apcmin mice and Apcmin-PD littermates at 8 weeks of age. Upper panel: Photomicrographs of whole-length intestinal sections (Swiss roll). Arrows indicate tumors. Lower panel: higher-magnification photomicrographs of tumor lesions. B, Intestinal tumor numbers and sizes for the indicated groups (n = 6 mice per group). Φ indicates tumor maximum diameter. C-E, Effects of PPARD overexpression on intestinal tumorigenesis in APCΔ580 mice. C, Representative images of H&E-stained whole-length intestinal sections of ApcΔ580 and ApcΔ580-PD mice at 14 weeks of age. Upper and lower panel picture descriptions are similar to panel A. D, Intestinal tumor numbers and sizes for the indicated groups (n = 15 mice per group). E, Survival curves of ApcΔ580 and ApcΔ580-PD mice (n = 20 mice per group). F-H, Effects of PPARD agonist GW501516 on intestinal tumorigenesis in ApcΔ580 mice. F, ApcΔ580 mice at age 4 weeks were fed a diet containing 50 mg/kg GW501516 (ApcΔ580-GW) or a control diet (ApcΔ580-Ctrl) for 10 weeks and then killed for intestinal tumorigenesis analyses. Upper and lower panel picture descriptions are similar to panel A. G, Intestinal tumor numbers and sizes for the indicated groups (n = 10 mice per group). H, Survival curves of the indicated groups (n = 12 mice per group). I and J, Effects of PPARD overexpression on intestinal tumorigenesis driven by adult-onset intestinally targeted APC mutation. ApcΔ580 mutation was induced in the mice at age 6 weeks via tamoxifen-controlled Cre-recombinase expression driven by CDX-2 promoter (ApcΔ580-TMX). ApcΔ580-TMX mice without or with intestinal PPARD overexpression (ApcΔ580-TMX-PD) were followed for 55 weeks before they were killed for intestinal tumorigenesis analyses. I, Upper and lower panel picture descriptions are similar to panel A. J, Intestinal tumor numbers and sizes for the indicated groups (n = 8 mice per group). K and L, Effects of PPARD knockout/deletion on intestinal tumorigenesis in APCΔ580 mice. Representative colon photographs (K) and colonic tumor numbers and sizes (L) of ApcΔ580 and ApcΔ580-PD-KO mice at 14 weeks of age (n = 8 mice per group). M and N, Effects of PPARD antagonist GSK3787 on intestinal tumorigenesis in ApcΔ580 mice. ApcΔ580 mice at age 4 weeks were fed a diet containing 200 mg/kg GSK3787 (ApcΔ580-GSK) or a control diet (ApcΔ580-Ctrl) for 12 weeks and then killed for intestinal tumorigenesis analyses. Representative colon photographs (M) and colonic tumor numbers and sizes (N) for the indicated groups (n = 18-20 mice per group). Data are shown as mean ± SEM. *P < 0.05, **P < 0.01, and ***P < 0.001.