Pancreatic ductal adenocarcinoma (PDA) is characterized by near universal mutations in the Kras proto-oncogene. Targeting constitutively active Kras to the pancreas results in the development of preneoplastic lesions and malignant progression similar to that observed in human PDA. Here we explore the capacity of mutant Kras to initiate PDA by reprogramming pancreatic acinar cells into a lineage that resembles human pancreatic intraepithelial neoplasia (PanIN), believed to be the most common route to PDA in man. Chronic pancreatitis is a major risk factor for human PDA, and chemically induced pancreatitis provides a permissive environment for PanIN and PDA formation in mouse models driven by mutant Kras. We found that mutant Kras dramatically alters the plasticity of acinar cells, preventing regeneration at the expense of a normally restricted, persistently ductal cell fate capable of giving rise to PanINs. Unlike acinar regeneration, which is characterized by activation of Beta-catenin signaling, Beta-catenin signaling is inhibited during early stages of Kras driven metaplasia. Using gain and loss of function approaches, we found that Beta-catenin is required for acinar regeneration and that enforced stabilization of Beta-catenin antagonizes acinar to ductal reprogramming that can give rise to PanINs. Therefore, Kras dependent specification of acinar derived PanINs depends on critical temporal thresholds of Beta-catenin signaling. Continuing the theme of Kras altering pancreatic plasticity, we investigated the role of miRNA processing in Kras driven PDA initiation. We found that deleting the critical miRNA biogenesis enzyme Dicer in the pancreas in the context of mutant Kras dramatically accelerates ductal metaplasia. However, this does not result in accelerated development of PanIN or PDA, and Dicer deficient cells do not contribute to PDA in mice. Dicer deficient acini display compromised expression of markers of acinar differentiation, which provides a permissive environment for Kras dependent ductal reprogramming. However, this differentiation state is unstable and displays considerable apoptosis, likely preventing the cells from contributing to PDA development. Therefore, we hypothesize that miRNA expression must be appropriately tuned to both permit preneoplastic differentiation and maintain cellular viability during Kras driven pancreatic transformation.