In aggregate, these results demonstrate that the FoxO3a-Skp2-p27Kip1 pathway, first defined by our in vitro mechanistic experiments in cultured pancreatic cancer cells (Figure 3), associates with the Nupr1−/− genotype in vivo giving rise to OIS with a concomitant impairment in PanIN development. Here, CDKN1B is linked to familial pancreatic carcinoma.