C/EBP beta regulates homeostatic and oncogenic gastric cell proliferation

• Type: Article in International Scientific Journal
• Date: 2016

Authors

Regalo, G (Author) Other; Foerster, S (Author) Other; Resende, C (Author) Other; Bauer, B (Author) Other; Fleige, B (Author) Other; Kemmner, W (Author) Other; Schlag, PM (Author) Other; Meyer, TF (Author) Other; Machado JC (Author) FMUP; Leutz, A (Author) Other

Journal

Title: Journal of Molecular Medicine

Vol. 94

Pages: 1385-1395

ISSN: 0946-2716

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 14 Citations

Scopus - 16 Citations

Other information

Authenticus ID: P-00K-S22

DOI: 10.1007/s00109-016-1447-7

Abstract (EN): Cancer of the stomach is among the leading causes of death from cancer worldwide. The transcription factor C/EBP beta 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/EBP beta. Cross-species comparison of gene expression profiles between C/EBP beta-deficient murine stomach and human gastric cancer revealed a subset of tumors with a C/EBP beta 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/EBP beta and that cross-regulation between C/EBP beta-RUNX1t1-TFF1 plays an important role in gastric carcinogenesis. C/EBP beta controls proliferation and differentiation balance in the stomach. Homeostatic differentiation/proliferation balance is altered in gastric cancer. RUNX1t1 is a C/EBP beta-associated tumor suppressor. RUNX1t1 negatively regulates C/EBP beta pro-oncogenic functions.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11