Figure 2. Mutant Kras blocks acinar regeneration in favor of a persistently dedifferentiated state.

(A–H) Clusterin and Sox9 (I–P) expression during regeneration and Kras-induced ADM. (A and I) Clusterin expression is limited to some normal ducts in PBS-treated Pdx1-Cre^Early mice, while Sox9 is restricted to ducts and centroacinar cells (arrowheads). (E and M) Acini in PBS-treated Pdx1-Cre^Early;LSL-Kras^G12D mice are negative for Clusterin and Sox9, while normal ducts and spontaneous PanINs are positive (asterisks). (B, F, J, and N) Damaged duct-like cells of both genotypes display clusterin- and Sox9-positive cells (insets). (C, D, K, and L) Clusterin and Sox9 are mainly restricted to duct cells (arrowheads) following regeneration in Pdx1-Cre^Early pancreata. Rare clusterin-positive cells were observed 7 days following caerulein treatment (arrow, C). (G, H, O, and P) Clusterin and Sox9 remain strongly expressed in ADM and PanINs in Pdx1-Cre^Early;LSL-Kras^G12D mice. (Q) Schematic of failed regeneration of acini possessing mutant Kras (acini*) versus WT. WT acini transiently dedifferentiate and rapidly regenerate, while acini possessing mutant Kras are sensitized to persistent dedifferentiation and ADM/PanIN formation. Original magnification, ×400 (A–P; insets).