Fig. 3: Loss of wild-type Kras increases mutant KRAS-driven tumourigenesis together with Apc loss. | Nature Communications

Fig. 3: Loss of wild-type Kras increases mutant KRAS-driven tumourigenesis together with Apc loss.

From: KRAS allelic imbalance drives tumour initiation yet suppresses metastasis in colorectal cancer in vivo

Fig. 3: Loss of wild-type Kras increases mutant KRAS-driven tumourigenesis together with Apc loss.

a Kaplan–Meier survival curve of villin-creERT2 Apc+/fl Kras+/G12D (AKras+/G12D) and villin-creERT2 Apc+/fl Krasfl/G12D (AKrasfl/G12D) mice aged until clinical endpoint (Apc+/fl Kras+/G12D, n = 8, 5M, 3F, MS, median survival = 63; Apc+/fl Krasfl/G12D, n = 9, 5M, 4F, MS, median survival = 25), ****P = 7.5 × 10-5, log-rank (Mantel-Cox) test. b Left: Boxplots showing total number of tumours from Apc+/fl Kras+/G12D and Apc+/fl Krasfl/G12D mice aged until clinical endpoint in SI and Colon. Right: Boxplots showing tumour area (mm2) and tumour size (mm2) in Apc+/fl Kras+/G12D and Apc+/fl Krasfl/G12D mice aged until clinical endpoint. Boxes depict interquartile range, central line indicates median and whiskers indicate minimum/maximum values (Apc+/fl Kras+/G12D, n = 7, 5M, 2F; Apc+/fl Krasfl/G12D n = 5, 3M, 2F). **P = 0.0013 (SI), **P = 0.0013 (colon), *P = 0.036 (area), **P = 0.0088 (size), one-way Mann–Whitney U test. c Representative H&E images of AKras+/G12D (n = 5, 2M, 3F) and AKrasfl/G12D (n = 8, 5M, 3F) tumour. Dashed box highlights selected area shown in high magnification. d Representative images of nuclear β-catenin and pERK1/2 staining in Apc+/fl Kras+/G12D (n = 5, 2M, 3F) and Apc+/fl Krasfl/G12D (n = 8, 5M, 3F) tumours at clinical endpoint. Scale, 100 µm. e Representative images of γH2AX and c-MYC staining in Apc+/fl Kras+/G12D (n = 5, 2M, 3F) and Apc+/fl Krasfl/G12D (n = 8, 5M, 3F) tumours at clinical endpoint. Scale, 100 µm. f H-score of γH2AX (Apc+/fl Kras+/G12D, n = 6, 4M, 2F; Apc+/fl Krasfl/G12D n = 5, 3M, 2F) and c-MYC (Apc+/fl Kras+/G12D, n = 5, 2M, 3F; Apc+/fl Krasfl/G12D n = 8, 5M, 3F) IHC staining of (e). Boxes depict interquartile range, central line indicates median and whiskers indicate minimum/maximum values. **P = 0.0043, ***P = 0.0008, one-way Mann–Whitney U test. g Representative BrdU staining of Apc+/fl Kras+/G12D and Apc+/fl Krasfl/G12D small intestinal tumours at clinical endpoint. Scale, 100 µm. Right: quantification of BrdU positivity in tumour cells. Boxes depict interquartile range, central line indicates median and whiskers indicate minimum/maximum values. (Apc+/fl Kras+/G12D, n = 5, 3M, 2F; Apc+/fl Krasfl/G12D n = 4, 2M, 2F). *P = 0.0317, one-way Mann–Whitney U test. Source data are provided as a Source Data file.

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