Recent work suggested that inhibition of MEK/ERK signaling promotes the regression of PanIN lesions . As determined by immunohistochemical staining for phosphorylated ERK, we observed that 17KC PanINs display marked reduction in MAPK signaling (Figure 2A–2D). In contrast to the difference in phosphorylated ERK, phosphorylation of the upstream kinase MEK was not different between the two genotypes, suggesting that signaling through the MEK/ERK cascade is impacted at the level of ERK but not further upstream (Figure 2E–2H). Moreover, ectopic mir-17~92 expression in murine PanIN cell lines [46, 47] increased p-ERK levels under both serum replete and serum starved conditions (Figure 3A, 3B), confirming that mir-17~92-encoded miRNAs regulate this pathway.