| Literature DB >> 22264787 |
Michael Quante1, Govind Bhagat, Julian A Abrams, Frederic Marache, Pamela Good, Michele D Lee, Yoomi Lee, Richard Friedman, Samuel Asfaha, Zinaida Dubeykovskaya, Umar Mahmood, Jose-Luiz Figueiredo, Jan Kitajewski, Carrie Shawber, Charles J Lightdale, Anil K Rustgi, Timothy C Wang.
Abstract
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 signaling.Entities:
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Year: 2012 PMID： 22264787 PMCID： PMC3266546 DOI： 10.1016/j.ccr.2011.12.004
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743