Author/Authors :
Quante، نويسنده , , Michael and Bhagat، نويسنده , , Govind and Abrams، نويسنده , , Julian A. and Marache، نويسنده , , Frederic and Good، نويسنده , , Pamela and Lee، نويسنده , , Michele D. and Lee، نويسنده , , Yoomi and Friedman، نويسنده , , Richard and Asfaha، نويسنده , , Samuel and Dubeykovskaya، نويسنده , , Zinaida and Mahmood، نويسنده , , Umar and Figueiredo، نويسنده , , Jose-Luiz and Kitajewski، نويسنده , , Jan and Shawber، نويسنده , , Carrie and Lightdale، نويسنده , , Charles J. and Rustgi، نويسنده , , Anil K. and Wang، نويسنده , , Timothy C.، نويسنده ,
Abstract :
Summary
geal 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 signaling.
