A cell autonomous EGFR-NFATc1 loop promotes acinar to ductal metaplasia in pancreatic carcinogenesis

Introduction: Recent evidence has shown a crucial role for EGFR activation in KrasG12 D -driven pancreatic carcinogenesis. However, the key transcription pathways conferring EGFR signalling in early tumorigenesis are enigmatic. Aims: To define signaling networks in EGFR driven ADM formation in vitro and in vivo. Methods: KrasG12 D mice strains with pancreas specific differential NFATc1 activation were challenged by chronic pancreatitis. Acinar cells were isolated from KrasG12D or KrasG12 D-NFATc1fl/fl mice and treated with EGF (20 ng/ml). Pancreata and acinar cell explants were analysed by IHC, RT-PCR and WB. Ch…