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. Author manuscript; available in PMC: 2015 Jan 1.
Published in final edited form as: Toxicol Pathol. 2013 Oct 31;42(1):217–228. doi: 10.1177/0192623313508250

Figure 3. Acinar reprogramming in PDAC initiation.

Figure 3

PDAC originates from differentiated acinar cells, in which KRAS mutation alone does not elevate total RAS activity to the levels required for transformation. Acinar-ductal reprogramming occurs when KRAS signaling increases in response to exogenous inflammatory stimuli and/or EGFR agonists; as KRAS activity increases, mutant cells produce endogenous signals that establish a positive feedback loop between KRAS and inflammation. Several genes counteract acinar reprogramming, including Nr5a2, Mist1 and β-catenin, but are themselves inhibited by high levels of KRAS signaling. We hypothesize that acinar reprogramming represents a key step of PDAC initiation, which might be inhibited by anti-inflammatory agents in a chemopreventive setting.