title: C/EBPβ regulates homeostatic and oncogenic gastric cell proliferation.
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/EBPβ 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.
  
  
  
  C/EBPβ controls proliferation and differentiation balance in the stomach. Homeostatic differentiation/proliferation balance is altered in gastric cancer. RUNX1t1 is a C/EBPβ-associated tumor suppressor. RUNX1t1 negatively regulates C/EBPβ pro-oncogenic functions.
authors: Max-Delbrueck-Center for Molecular Medicine, Robert-Roessle-Str. 10, 13125, Berlin, Germany. goncalo.regalo@mdc-berlin.de.
authors: Goncalo
authors: G
authors: Regalo
authors: Max-Delbrueck-Center for Molecular Medicine, Robert-Roessle-Str. 10, 13125, Berlin, Germany.
authors: Susann
authors: S
authors: Förster
authors: Institute of Pathology and Molecular Immunology of the University of Porto, 4200-465, Porto, Portugal.
authors: Carlos
authors: C
authors: Resende
authors: Max-Planck Institute for Infection Biology, 10117, Berlin, Germany.
authors: Bianca
authors: B
authors: Bauer
authors: Institut für Gewebediagnostik Berlin am MVZ des HELIOS Klinikum, 13125, Berlin, Germany.
authors: Barbara
authors: B
authors: Fleige
authors: Max-Delbrueck-Center for Molecular Medicine, Robert-Roessle-Str. 10, 13125, Berlin, Germany.
authors: Wolfgang
authors: W
authors: Kemmner
authors: Charité Comprehensive Cancer Centers, Charité-Universitätsmedizin, 10117, Berlin, Germany.
authors: Peter M
authors: PM
authors: Schlag
authors: Max-Planck Institute for Infection Biology, 10117, Berlin, Germany.
authors: Thomas F
authors: TF
authors: Meyer
authors: Institute of Pathology and Molecular Immunology of the University of Porto, 4200-465, Porto, Portugal.
authors: José C
authors: JC
authors: Machado
authors: Max-Delbrueck-Center for Molecular Medicine, Robert-Roessle-Str. 10, 13125, Berlin, Germany. aleutz@mdc-berlin.de.|Humboldt-University of Berlin, Institute of Biology, 10115, Berlin, Germany. aleutz@mdc-berlin.de.
authors: Achim
authors: A
authors: Leutz
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005753:Gastric Mucosa / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D000075142:RUNX1 Translocation Partner 1 Protein / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000071163:Trefoil Factor-1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; C545012:CEBPB protein, human; C545013:Cebpb protein, mouse; D034741:RNA, Small Interfering; D000075142:RUNX1 Translocation Partner 1 Protein; C082222:RUNX1T1 protein, human; C051838:TFF1 protein, human; D000071163:Trefoil Factor-1
keywords: C/EBPβ; Gastric cancer; Homeostasis; Proliferation; RUNX1t1; TFF1