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. 2022 Apr 13;41(20):2811–2823. doi: 10.1038/s41388-022-02302-0

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 5 — A Kaplan–Meier curves. Cohorts consisted of the following genotypes: Kras^+/+; Ptf1a-Cre; Dusp^+/+ (Ptf1a-Cre), Kras^LSL-G12D/+; Ptf1a-Cre; Dusp^+/+ (KC), Kras^LSL-G12D/+; Ptf1a-Cre; Dusp5^+/fl (KCD5^+/−), Kras^LSL-G12D/+; Ptf1a-Cre; Dusp5^fl/fl (KCD5^−/−), Kras^LSL-G12D/+; Ptf1a-Cre; Dusp6^+/fl (KCD6^+/−) and Kras^LSL-G12D/+; Ptf1a-Cre; Dusp6^fl/fl (KCD6^−/−) Left panel, overall survival n = 12, 21, 14, 27, 15 and 22, respectively. Log-rank test: KC versus KCD5^−/− ****p < 0.0001, KC versus KCD6^−/− ****p < 0.0001. Right panel, PDAC-free survival n = 12, 0 censored; 21, 3 censored; 14, 3 censored; 27, 17 censored; 15, 3 censored and 22, 11 censored, respectively. The majority of mice were censored due to severe weight loss without PDAC, with the remainder censored due to extra-pancreatic pathologies such as skin wounds and prolapse. Log-rank test: KC versus KCD5^−/− ns, KC versus KCD6^−/− *p < 0.05. B Representative images of H&E staining (left panels), cytokeratin-19 IHC (CK19, middle panels) and Ki67 IHC (right panels) of either well-differentiated or poorly-differentiated PDAC tissue, taken from tumours in either KC or KCD6^−/− mice. (Scale bars, 500 μm.) C Quantification of the percentage of Ki67-positive cells in PDAC tumour sections taken from six mice of the indicated cohorts. Based on morphology, these are designated as either well- or poorly-differentiated tumours. Individual data points and mean are shown, n = 6, ns not significant, *p < 0.05 using one-way ANOVA and Bonferroni post hoc test. D Quantification of the percentage of tumour-bearing mice that displayed poorly-differentiated PDAC of the indicated cohorts. E Representative images of H&E staining and PDX1 IHC of liver metastases presented by KC or KCD6^−/− mice. (Scale bars, KC, 800 μm and KCD6^−/− 300 μm.) F The percentage of mice presenting with PDAC of the indicated cohorts that displayed associated liver metastasis. D, F n = 18, 8, 8, 9 and 10, ns not significant, *p < 0.05 using a 2 × 2 contingency table analysed by Fisher’s exact test with a two-tailed p value.