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. 2014 Dec 1;28(23):2621–2635. doi: 10.1101/gad.249409.114

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© 2014 Baer et al.; Published by Cold Spring Harbor Laboratory Press

This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.

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Figure 2. — Genetic inactivation of p110α catalytic activity in the pancreas prevents the development of mutated Kras-induced pancreatic preneoplastic and neoplastic lesions. (A) Experimental setup to express kinase-dead p110α and oncogenic Kras^G12D in the pancreas. (B) Survival curve. Expected Mendelian ratios for Cre⁺;p110α^lox/lox were found; total number of pups was 155. N > 10 per genotype. (C) Percentage of 6-mo-old mice harboring no lesions, ADM, or PanINs depending on genotypes. (D) Representative H&E stains (insets show representative areas in high magnification; scale, 500 or 100 μm) and indicated IHC analysis on paraffin-embedded KC, KC;p110α^+/lox, and KC;p110α^lox/lox pancreata. (Arrowheads) Pancreatic lobules with stromal Ki67-positive cells present in areas of ADM ; (em) early metaplastic transitions; (*) ADM lesions; (#) low-grade PanIns; (red arrowheads) CK19-positive normal ducts. CK19 is a well-defined ductal cell marker overexpressed first at the basolateral membrane of acinar cells (em) (Zhu et al. 2007) that undergo ADM. N = 4. (E) Pancreatic sections of KC, KC;p110α^+/lox, and KC;p110α^lox/lox animals were analyzed for the presence of pS473Akt, pAkt substrate, and pThr202/Tyr204ERK1/2 (cytoplasmic and nuclear staining) by IHC on serial sections (4 μm). Slides were counterstained with hematoxylin. Representative pictures are shown (N = 4). Scale, 100 μm. (F) Experimental setup to express kinase-dead p110β and oncogenic Kras^G12D in the pancreas. (G) Percentage of 6-mo-old mice harboring no lesions, ADM, or PanINs depending on genotypes. (H) H&E.