Figure 3. Crypt hyperplasia is Mek-dependent.
- Treatment regime. Braf+/LSL-V600E; AhcreERT+/o were treated with β-NF followed by β-NF + TM 24 h later. At 1, 2 and 3 days p.i., half of the induced mice were administered with 200 mg/kg PD184352 by intraperitoneal injection. Mice were sacrificed 6 h after the last injection. WT mice were also subjected to the same dose of PD184352 for 3 days.
- Erk phosphorylation is inhibited by PD184352. Protein lysates were prepared from the small intestine of all mice and subjected to Western blot analysis with an antibody for phospho-Erk. Erk2 was used as a loading control.
- PD184352 reverses crypt hyperplasia. H&E-stained ‘swiss’ rolls of section 1 (ileum) were scored blind for number of cells per full crypt. Ninety-four crypts from three VE animals ± PD184352 and three WT animals without PD184352 were counted. Fifty crypts from WT animals + PD184352 were also counted but did not give an altered distribution compared to WT animals without treatment (data not shown). Data are presented as the frequency with which a given number of cells/crypt is represented amongst the crypts counted. The mean frequency for each genotype/treatment is shown.