Obstructive CP promotes tumorigenesis from duct cells but not from acinar cells. Mice were subjected to PDL 1 month after tamoxifen treatment and then followed for up to 4 months. (A–C) Pancreas distal to ligation (tail region) from mice with no Kras mutation (A) or KrasG12D mutation specifically in acinar cells (B) or ductal cells (C) 4 months after PDL. (A’, B’, and C’) show corresponding pancreata proximal to ligation (head region). (D) H&E staining of lesions in CK19CreERT2LSL-KrasG12DR26REYFP mouse 2 months after PDL. Note that no invasion was observed at this time point, but atypia occurred focally. (E and F) EYFP immunostaining CK19CreERT2LSL-KrasG12DR26REYFP mice showing early invasion. (G) Some CK19CreERT2LSL-KrasG12D lesions have high proliferative index as shown by Ki67 immunohistochemistry (G). (H and I) H&E staining of two Sox9-CreERT LSL-KrasG12DR26REYFP distal pancreata showing extensive invasion 8–10 months after PDL. (J–L) H&E staining of liver metastatic lesions from Sox9-CreERT LSL-KrasG12D mouse 10 months after PDL showing low magnification of a large lesion (J), a micrometastasis (K), and high magnification within a different large metastasis. Size bars, 100 μm. met, metastasis; WT, wild-type.