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C/EBPβ regulates homeostatic and oncogenic gastric cell proliferation

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Item Type:Article
Title:C/EBPβ regulates homeostatic and oncogenic gastric cell proliferation
Creators Name:Regalo, G. and Förster, S. and Resende, C. and Bauer, B. and Fleige, B. and Kemmner, W. and Schlag, P.M. and Meyer, T.F. and Machado, J.C. and Leutz, A.
Abstract:Cancer of the stomach is among the leading causes of death from cancer worldwide. The transcription factor C/EBPβ is frequently overexpressed in gastric cancer and associated with the suppression of the differentiation marker TFF1. We show that the murine C/EBP{beta} knockout stomach displays unbalanced homeostasis and reduced cell proliferation and that tumorigenesis of human gastric cancer xenograft is inhibited by knockdown of C/EBPβ. Cross-species comparison of gene expression profiles between C/EBPβ-deficient murine stomach and human gastric cancer revealed a subset of tumors with a C/EBPβ signature. Within this signature, the RUNX1t1 tumor suppressor transcript was down-regulated in 38% of gastric tumor samples. The RUNX1t1 promoter was frequently hypermethylated and ectopic expression of RUNX1t1 in gastric cancer cells inhibited proliferation and enhanced TFF1 expression. These data suggest that the tumor suppressor activity of both RUNX1t1 and TFF1 are mechanistically connected to C/EBPβ and that cross-regulation between C/EBPβ-RUNX1t1-TFF1 plays an important role in gastric carcinogenesis.
Keywords:C/EBPβ, RUNX1t1, Gastric Cancer, TFF1, Proliferation, Homeostasis, Animals, Mice
Source:Journal of Molecular Medicine
Page Range:1385-1395
Date:December 2016
Official Publication:https://doi.org/10.1007/s00109-016-1447-7
PubMed:View item in PubMed

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