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. Author manuscript; available in PMC: 2021 Sep 1.
Published in final edited form as: Cancer Discov. 2021 Mar;11(3):660–677. doi: 10.1158/2159-8290.CD-20-0633

Figure 3. Pancreatic cancer can develop from adult mouse ductal cells.

Figure 3.

(A) Schematic for ductal cell-derived pancreatic cancer study of KT;Sox9CreER;Trp53+/+and KT;Sox9CreER;Trp53fl/fl mouse cohorts. Mice were treated with tamoxifen for 3 consecutive days at 8-10 weeks of age, then aged to analyze survival.

(B) Representative co-immunofluorescence staining for tdTomato (TOM) and amylase (AMY; acinar cell marker), cytokeratin 19 (CK19; ductal cell marker), and insulin (INS; islet marker), in a Rosa26LSL-tdTomato/LSL-tdTomato;Sox9CreER;Trp53+/+ mouse pancreas 3 days after the last dose of tamoxifen (n = 4). DAPI stains nuclei. Scale Bar = 50 μm.

(C) Kaplan-Meier analysis of pancreatic cancer-free survival of cohorts listed in (A). Labels indicate the Trp53 status of each cohort. Pancreatic cancer-free survival in KT;Sox9CreER;Trp53fl/fl mice (n = 25) is significantly different from that of KT;Sox9CreER;Trp53+/+ mice (n = 18), based on the log-rank test. ***p-value < 0.001.

(D) Kaplan-Meier analysis of overall survival of cohorts listed in (A). Labels indicate the Trp53 status of each cohort. Overall survival in KT;Sox9CreER;Trp53fl/fl mice (n = 25) is significantly different from that of KT;Sox9CreER;Trp53+/+ mice (n = 18), based on the log-rank test. ****p-value < 0.0001.

(E) Table summarizing the percentages of pancreatic tumor-bearing KT;Sox9CreER;Trp53fl/fl mice presenting with clinical symptoms of pancreatic cancer (ascites and bowel obstruction) at morbidity (n = 9).

(F) Table summarizing the percentages of tumor-bearing KT;Sox9CreER;Trp53fl/fl mice (n = 9) with primary tumor grade (comprising > 50% of the tumor) of moderately/well-differentiated or poorly-differentiated adenocarcinomas. KT;Sox9CreER;Trp53+/+ mice (n = 18) had no evidence of pancreatic tumors.

(G) Representative histological images of typical pancreas morphology found in each cohort, analyzed by H&E staining and immunohistochemistry for tdTomato and CK19. Scale Bar = 100 μm.

(H) Representative image of a peritoneum metastasis in a KT;Sox9CreER;Trp53fl/fl mouse analyzed by H&E staining and immunohistochemistry for tdTomato and CK19. Scale Bar = 100 μm.