Figure 3. p21 loss following Apc deletion leads to rapid onset of renal tumourigenesis.

A. Kaplan–Meier survival graph showing a dramatic acceleration of renal tumourigenesis in AhCre⁺ Apc^fl/fl p21^−/− mice (Apc p21^−/−, n = 31, median lifespan 63 days, blue line) compared with AhCre⁺ Apc^+/+ (Wt n = 20, <400 days) and AhCre⁺ Apc^fl/fl mice (Apc, n = 23, red line, Log rank v Apc^fl/fl p21^−/−, p < 0.001). Note there was a marked acceleration of tumourigenesis in AhCre⁺ Apc^fl/fl p21^+/− mice (Apc p21^+/− median lifespan 117 days, n = 17, green line, Log rank v Apc^fl/fl p < 0.001).

B. H&E of a renal tumour in AhCre⁺ Apc^fl/fl p21^−/− mice.

C–E. Staining shows absence of senescent markers SA β-gal (C), p16 (D) and p21 (E) in AhCre⁺ Apc^fl/fl p21^−/− renal tumours. Note there is a small amount non-specific brown staining in the p21 knockout tumours when p21 IHC is performed (black arrow), however all nuclei are blue showing a complete loss of p21 within the tumours (red arrow).

F. β-catenin IHC showing continued Wnt signalling activation in AhCre⁺ Apc^fl/fl p21^−/− deficient renal tumours.

G and H Ki67 IHC (G) and MCM2 IHC (H) showing a marked increase in proliferation in AhCre⁺ Apc^fl/fl p21^−/− deficient tumours. Scale bars represent 200 µm.