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. 2023 Apr 16;83(12):1953–1967. doi: 10.1158/0008-5472.CAN-22-3848

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©2023 The Authors; Published by the American Association for Cancer Research

This open access article is distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license.

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Figure 3. Mutation of Keap1 or Nrf2 is not sufficient to initiate lung tumorigenesis with p53 or Lkb1 loss. A, Overall survival of p53fl/fl mice expressing WT or mutant Keap1/Nrf2. Keap1/Nrf2+/+ (n = 15); Keap1R554Q/+ (n = 7); Keap1R554Q/R554Q (n = 18); Nrf2D29H/+ (n = 18). ns, not significant [log-rank (Mantel–Cox) test]. B, Lung tumor-free survival of p53fl/fl mice expressing WT or mutant Keap1/Nrf2. Keap1/Nrf2+/+ (n = 11); Keap1R554Q/+ (n = 6); Keap1R554Q/R554Q (n = 16); Nrf2D29H/+ (n = 10). C, Representative hematoxylin and eosin staining of mouse lung depicting bronchiolar and alveolar cells of the p53fl/fl models. Scale bars, 100 μm (top), 20 μm (middle), and 10 μm (bottom). D, Overall survival of Lkb1fl/fl mice expressing WT or mutant Keap1/Nrf2. Keap1/Nrf2+/+ (n = 11); Keap1R554Q/+ (n = 7); Keap1R554Q/R554Q (n = 11); Nrf2D29H/+ (n = 5). ns, not significant [log-rank (Mantel–Cox) test]. E, Lung tumor-free survival of Lkb1fl/fl mice expressing WT or mutant Keap1/Nrf2. Keap1/Nrf2+/+ (n = 11); Keap1R554Q/+ (n = 6); Keap1R554Q/R554Q (n = 9); Nrf2D29H/+ (n = 4). F, Representative hematoxylin and eosin staining of mouse lung depicting bronchiolar and alveolar cells of the Lkb1fl/fl models. Scale bars, 100 μm (top), 20 μm (middle), and 10 μm (bottom). A, B, D, and E, Mice were infected intranasally with adenoviral-Cre, followed by collection at 500 days to analyze lung tissue histology. — Mutation of Keap1 or Nrf2 is not sufficient to initiate lung tumorigenesis with p53 or Lkb1 loss. A, Overall survival of p53^fl/fl mice expressing WT or mutant Keap1/Nrf2. Keap1/Nrf2^+/+ (n = 15); Keap1^R554Q/+ (n = 7); Keap1^R554Q/R554Q (n = 18); Nrf2^D29H/+ (n = 18). ns, not significant [log-rank (Mantel–Cox) test]. B, Lung tumor-free survival of p53^fl/fl mice expressing WT or mutant Keap1/Nrf2. Keap1/Nrf2^+/+ (n = 11); Keap1^R554Q/+ (n = 6); Keap1^R554Q/R554Q (n = 16); Nrf2^D29H/+ (n = 10). C, Representative hematoxylin and eosin staining of mouse lung depicting bronchiolar and alveolar cells of the p53^fl/fl models. Scale bars, 100 μm (top), 20 μm (middle), and 10 μm (bottom). D, Overall survival of Lkb1^fl/fl mice expressing WT or mutant Keap1/Nrf2. Keap1/Nrf2^+/+ (n = 11); Keap1^R554Q/+ (n = 7); Keap1^R554Q/R554Q (n = 11); Nrf2^D29H/+ (n = 5). ns, not significant [log-rank (Mantel–Cox) test]. E, Lung tumor-free survival of Lkb1^fl/fl mice expressing WT or mutant Keap1/Nrf2. Keap1/Nrf2^+/+ (n = 11); Keap1^R554Q/+ (n = 6); Keap1^R554Q/R554Q (n = 9); Nrf2^D29H/+ (n = 4). F, Representative hematoxylin and eosin staining of mouse lung depicting bronchiolar and alveolar cells of the Lkb1^fl/fl models. Scale bars, 100 μm (top), 20 μm (middle), and 10 μm (bottom). A, B, D, and E, Mice were infected intranasally with adenoviral-Cre, followed by collection at 500 days to analyze lung tissue histology.