The mechanisms underlying the regulation of ERK activity by mir-17~92 are unknown. We explored the possibility that mir-17~92 increases ERK activation via suppression of dual-specificity phosphatases (DUSPs), which are well-known regulators of numerous MAPK family proteins, including ERK . In particular, DUSP2, DUSP7 and DUSP10 suppress ERK activity and are demonstrated or predicted targets of mir-17~92 miRNAs [48, 58–60]. Interestingly, a recent publication linked miR-92 and DUSP10 to PDAC cell proliferation in vitro, suggesting that there may indeed be an important role for this regulatory axis in pancreatic tumorigenesis . However, immunohistochemical staining of DUSP2, DUSP7 and DUSP10 failed to demonstrate any difference between KC and 17KC PanIN lesions, and modulation of mir-17~92 levels in PanIN cell lines also failed to change the levels of these phosphatases. Thus, the precise mechanisms through which mir-17~92 regulates ERK phosphorylation remain unknown. Additional studies using inducible expression or repression of mir-17~92 miRNAs, coupled to mRNA and proteomic profiling approaches, will aid in elucidating the mechanisms by which this cluster regulates ERK phosphorylation in the early stages of pancreatic tumorigenesis.