Activation of KrasG12D and Tgfa leads to an accelerated carcinogenesis and the develoment of IPMN lesions in a novel endogenous mouse model of pancreatic cancer

Introduction: Besides activation of an oncogenic KrasG12D mutation, growth factors have been implicated in pancreatic carcinogenesis. In this study we analyzed the effect of pancreas-specific Tgfa overexpression in addition to conditional activation of mutant endogenous KrasG12D. Methods: Elastase-Tgfa mice were crossed to p48+/Cre;Kras+/LSL-G12D mice. Pancreata were analyzed at different time points and after development of malignant tumors using IHC, IF, WB, quantitative RT-PCR and Affymetrix array. Results: Concomitant expression of Tgfa and mutated KrasG12D leads to an accelerated progression of mPanIN lesio…