Figure 1 from <i>KRAS</i> Loss of Heterozygosity Promotes MAPK-Dependent Pancreatic Ductal Adenocarcinoma Initiation and Induces Therapeutic Sensitivity to MEK Inhibition
Authors: Fey Sigrid K. , Najumudeen Arafath K. , Watt Dale M. , Millett Laura M. , Ford Catriona A. , Gilroy Kathryn , Simpson Rosalin J. , McLay Kathy , Upstill-Goddard Rosanna , Chang David , Clark William , Nixon Colin , Birch Joanna L. , Barry Simon T. , Morton Jennifer P. , Campbell Andrew D. , Sansom Owen J. 
Published: January 2025

<p>Loss of WT <i>Kras</i> increases PanIN formation in the presence of oncogenic <i>Kras</i>. <b>A,</b> Kaplan–Meier survival curve for human patients with PDAC with <i>KRAS</i> alleles balanced and <i>KRAS</i> alleles imbalanced. KRAS balanced, <i>n</i> = 47; KRAS imbalanced, <i>n</i> = 32. *, <i>P</i> = 0.029, log-rank (Mantel–Cox) test. <b>B,</b> Proportion of human patients with pancreatic cancer with <i>KRAS</i> alleles balanced (59.5%) and <i>KRAS</i> alleles imbalanced (40.5%), from <b>A</b>. <b>C,</b> Schematic representing generation of KC <i>Kras</i><sup>G12D/fl</sup> mice. <b>D,</b> Representative hematoxylin and eosin (H&E) images of pancreata from KC <i>Kras</i><sup>G12D/+</sup> and KC <i>Kras</i><sup>G12D/fl</sup> mice at 42 days of age, representative of six mice per group. Scale bar, 200 μm. <b>E,</b> Quantification and grading of PanINs from KC <i>Kras</i><sup>G12D/+</sup> and KC <i>Kras</i><sup>G12D/fl</sup> mice at 42 days of age from one whole hematoxylin and eosin section per mouse (<i>n</i> = 6 per group), represented by <b>D</b>. Boxes depict the IQR, the central line indicates the median, and whiskers indicate minimum/maximum values. **, <i>P</i> < 0.01; one-way Mann–Whitney <i>U</i> test. <b>F,</b> Quantification of the area of ADM per mm<sup>2</sup> pancreas over one whole hematoxylin and eosin section from KC <i>Kras</i><sup>G12D/+</sup> and KC <i>Kras</i><sup>G12D/fl</sup> mice at 42 days of age (<i>n</i> = 6 per group). Boxes depict the IQR, the central line indicates the median, and whiskers indicate minimum/maximum values. **, <i>P</i> < 0.0011; one-way Mann–Whitney <i>U</i> test. <b>G,</b> Left, representative IHC images of pERK1/2 of pancreata from KC <i>Kras</i><sup>G12D/+</sup> and KC <i>Kras</i><sup>G12D/fl</sup> mice at 42 days of age. Representative of six mice per group. Scale bar, 200 μm. Right, bar graphs showing quantification of pERK1/2-positive cells of the pancreatic epithelium of KC <i>Kras</i><sup>G12D/+</sup> and KC <i>Kras</i><sup>G12D/fl</sup> mice sampled at day 42 (KC <i>Kras</i><sup>G12D/+</sup>, <i>n</i> = 6; KC <i>Kras</i><sup>G12D/fl</sup>, <i>n</i> = 6). Data are the mean ± SEM. *, <i>P</i> = 0.0325; one-way Mann–Whitney <i>U</i> test. <b>H,</b> Left, representative images of ISH of <i>Dusp5</i> and <i>Dusp6</i> of pancreata from KC <i>Kras</i><sup>G12D/+</sup> and KC <i>Kras</i><sup>G12D/fl</sup> mice at 42 days of age. Representative of six mice per group. Scale bar, 200 μm. Right, quantification of <i>Dusp5</i> and <i>Dusp6 ISH</i> staining of pancreatic lesions (PanINs) of pancreata from KC <i>Kras</i><sup>G12D/+</sup> and KC <i>Kras</i><sup>G12D/fl</sup> mice at 42 days of age (KC <i>Kras</i><sup>G12D/+</sup>, <i>n</i> = 6; KC <i>Kras</i><sup>G12D/fl</sup>, <i>n</i> = 6). Data are the mean ± SEM. **, <i>P</i> = 0.0011 (<i>Dusp5</i>); **, <i>P</i> = 0.0022 (<i>Dusp6</i>); one-way Mann–Whitney <i>U</i> test. Cre, Cre recombinase; loxP, Cre-loxP recombination site.</p>