C/EBP alpha expression is associated with homeostasis of the gastric epithelium and with gastric carcinogenesis

• Type: Article in International Scientific Journal
• Date: 2010

Authors

Regalo, G (Author) Other; Resende, C (Author) Other; Wen, XG (Author) Other; Gomes, B (Author) Other; Duraes, C (Author) Other; Seruca, R (Author) FMUP; Carneiro F (Author) FMUP; Machado JC (Author) FMUP

Journal

Title: Laboratory Investigation

Vol. 90

Pages: 1132-1139

ISSN: 0023-6837

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 22 Citations

Scopus - 24 Citations

Other information

Authenticus ID: P-003-4G9

DOI: 10.1038/labinvest.2010.79

Abstract (EN): Transcription factors from the CCAAT/enhancer-binding protein (C/EBP) family are fundamental for the control of differentiation and proliferation of many adult tissues. C/EBP alpha has a crucial role in inducing terminal differentiation and is an established tumor suppressor gene in several cancer models. The objective of this study was to analyze the putative role of C/EBP alpha in gastric carcinoma (GC). We analyzed the expression of C/EBP alpha in normal and neoplastic gastric tissues, and assessed the role of C/EBP alpha on proliferation and differentiation of GC cells. In normal gastric mucosa, C/EBP alpha is expressed in the foveolar epithelium and co-localizes with the gastric differentiation marker trefoil factor 1 (TFF1). The expression of C/EBP alpha was found to be lost in 30% of GC cases. To evaluate the role of C/EBP alpha in cell proliferation and differentiation, we transfected GC cells with a full-length C/EBP alpha protein. We observed a significant decrease in proliferation in C/EBP alpha-transfected cells. This was accompanied by a decrease in Cyclin D1, an increase in P27 expression, and an increased expression of TFF1. Finally, we showed that inhibition of the Ras/MAPK pathway leads to increased C/EBP alpha and TFF1 expression, and decreased cell proliferation and cyclin D1 expression in GC cells. Our results suggest that C/EBP alpha (together with other members of the C/EBP family) has an active role in the control of differentiation and proliferation in normal gastric mucosa. In GC, loss of C/EBP alpha may be associated with the switch from a cellular differentiation to a cellular proliferation program, presumably as a consequence of Ras/MAPK pathway activation. Laboratory Investigation (2010) 90, 1132-1139; doi:10.1038/labinvest.2010.79; published online 12 April 2010

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8