c-Fos/ERK promotes the progression from pancreatic intraepithelial neoplasia to pancreatic ductal adenocarcinoma.

Pathogenesis of pancreatic ductal adenocarcinoma (PDAC) is thought to develop through the progression of precursor lesions, known as pancreatic intraepithelial neoplasias (PanIN). In the present study, we showed that c-Fos promoted proliferation, cell cycle and migration in pancreatic cancer cells. Caerulein was used to accelerate the pathogenesis of Pdx-cre; KrasG12D mice. During PanIN formation and development of PDAC, the expression of ERK and c-Fos increased concomitantly. When ERK activity was inhibited by U0126, the expression of c-Fos also decreased. Inactivation of ERK/c-Fos suppressed pancreatic lesions concurrently through proliferation, inflammation and apoptosis. Our findings suggest that the ERK/c-Fos pathway is required for PDAC initiation and progression.