Figure 7.
ATM deficiency enhances mPanIN formation but does not prevent KrasG12D-induced senescence. (A–C) Partial or total ATM deficiency does not abolish the induction of senescence (A, SA-βgal staining) or the expression of p16Ink4a (B) or p19Arf (C), in KrasG12D-induced pancreatic precancerous lesions. (Arrows indicate small ductal lesions and asterisks indicate mPanINs). (D,E) ATM deficiency increases areas containing low-grade mPanINs (H&E staining, arrows in (D) and Alcian Blue staining, arrows in E) in a dosage-dependent manner in KrasG12D pancreata. (F) Quantification of Alcian Blue+ lesions in 2–4 months old KC, KCATMΔ+ and KCATMΔΔ pancreata demonstrates that low grade mPanINs are more abundant in tissues carrying partial or total ATM-deficiency (*P < 0.05; error bars represent ± SEM values; n = 3–4 individual specimens per genotype, ordinary one-way ANOVA). (G,H) ATM deficiency increases areas of fibrosis (Sirius red staining of collagen fibrils, arrows in G) and areas containing macrophage infiltrates (F4/80 immunostaining, arrows in H) in KrasG12D pancreata. Pancreatic specimens are from 2–4 months old mice. Scale bars: 200 µm (E,G); 100 µm (D,H); 50 µm (A–C).