biostudies-literatureQuante MNIDDK NIH HHSNHLBI NIH HHSNCI NIH HHS36-51https://www.ebi.ac.uk/biostudies/studies/S-EPMC3266546biostudies-literatureUnknown21(1)Esophageal adenocarcinoma (EAC) arises from Barrett esophagus (BE), intestinal-like columnar metaplasia linked to reflux esophagitis. In a transgenic mouse model of BE, esophageal overexpression of interleukin-1β phenocopies human pathology with evolution of esophagitis, Barrett-like metaplasia and EAC. Histopathology and gene signatures closely resembled human BE, with upregulation of TFF2, Bmp4, Cdx2, Notch1, and IL-6. The development of BE and EAC was accelerated by exposure to bile acids and/or nitrosamines, and inhibited by IL-6 deficiency. Lgr5(+) gastric cardia stem cells present in BE were able to lineage trace the early BE lesion. Our data suggest that BE and EAC arise from gastric progenitors due to a tumor-promoting IL-1β-IL-6 signaling cascade and Dll1-dependent Notch signalingCancer cellBile acid and inflammation activate gastric cardia stem cells in a mouse model of Barrett-like metaplasia.PMC3266546T35 HL007616U54 CA126513R01 DK060758K07 CA132892R01CA120979U01 CA143056R01 CA136673R01 CA1209795U01 CA143056U54 CA163004R01DK0607581U54CA126513,P30-DK050306P01-CA098101P30 DK050306P01 CA098101Friedman RLee MDDubeykovskaya ZRustgi AKShawber CQuante MWang TCBhagat GMarache FAbrams JAGood PAsfaha SLightdale CJLee YFigueiredo JLKitajewski JMahmood UfalseBile acid and inflammation activate gastric cardia stem cells in a mouse model of Barrett-like metaplasia.Esophageal adenocarcinoma (EAC) arises from Barrett esophagus (BE), intestinal-like columnar metaplasia linked to reflux esophagitis. In a transgenic mouse model of BE, esophageal overexpression of interleukin-1β phenocopies human pathology with evolution of esophagitis, Barrett-like metaplasia and EAC. Histopathology and gene signatures closely resembled human BE, with upregulation of TFF2, Bmp4, Cdx2, Notch1, and IL-6. The development of BE and EAC was accelerated by exposure to bile acids and/or nitrosamines, and inhibited by IL-6 deficiency. Lgr5(+) gastric cardia stem cells present in BE were able to lineage trace the early BE lesion. Our data suggest that BE and EAC arise from gastric progenitors due to a tumor-promoting IL-1β-IL-6 signaling cascade and Dll1-dependent Notch signaling2012-01-01T00:00:00Z2012 Jan2026-04-30T19:02:29.16Z2019-03-27T00:48:27ZS-EPMC32665462226478710.1016/j.ccr.2011.12.004