Fig. 5: Oncogenic KRAS-driven MAPK signalling confers tolerance to epithelial TGFβ activation.
a Representative H&E and Alk5 ISH of small intestinal tissue from VilCreER;Apcfl/fl;KrasG12D/+;Alk5CA mice 3 days post-tamoxifen and daily treatment with vehicle or ALK5-inhibitor (ALK5i). Scale bar, 100 μm. b Quantification of BrdU-positive (left) and apoptotic (right) cells in mice described in a. n = 4 mice per group (BrdU scoring); n = 5 mice per group (apoptosis scoring). Data were ±s.e.m; P = 0.68 (BrdU), P = 0.15 (apoptosis); two-tail Mann–Whitney U-test. c Representative Itgβ6 ISH and p-ERK IHC on mice of the indicated genotypes 3 days post-tamoxifen. Scale bars, 100 μm. d Quantification of p-ERK-positive cells per crypt-villus unit in mice described in c. n = 5 per group. Data were ±s.e.m; P = 0.003. Two-tail Mann–Whitney U-test. e H&E staining of small intestinal tissue from VilCreER;Apcfl/fl;KrasG12D/+;Alk5CA mice 3 days post-tamoxifen and daily treatment with vehicle or MEK1/2 inhibitor (MEKi). Right panels show magnification of boxed areas in left panels, with apoptotic cells indicated by black arrowheads. Scale bar, 100 μm. f Quantification of BrdU-positive (left) and apoptotic (right) cells in mice described in e. n = 3 mice per group. Data were ± s.e.m. *P = 0.05; one-tail Mann–Whitney U-test.
