tPA is not expressed in metaplastic ducts and is not required for acinar-ductal metaplasia. A and B: Immunohistochemical analysis of the expression of tPA in non-neoplastic ductal complexes. Sections of paraffin-embeded pancreatic tissues containing non-neoplastic ductal complexes were used to examine tPA (A and B) expression in pancreatic tissue from Ela1-myc (A) and MT-TGF-α mice (B). tPA was undetectable in ductal complexes (A and B, left) but it was present in tumor cells (A, right) and endothelial cells (B). Inset in A shows the lack of tPA expression in ductal complexes from Ela1-myc pancreatic tissue using higher magnification. C and D: Pancreatic duct ligation in wild-type and tPA−/− mice. Metaplastic ducts were observed in mice of both genotypes (C and D), indicating that tPA is not required for acinar-ductal metaplasia. Insets show the ductal complexes appearing after duct ligation. Original magnification; ×100 (A–D), ×400 (inset, B), ×200 (insets, C and D).