C/EBPbeta is over‐expressed in gastric carcinogenesis and is associated with COX‐2 expression

The CCAAT/enhancer‐binding protein beta (C/EBPbeta) transcription factor has been associated with several cancer models. In this study, the expression of C/EBPbeta was analysed in a series of 90 gastric carcinomas (GCs). We also assessed the effect of C/EBPbeta on COX‐2 expression. In normal gastric mucosa, C/EBPbeta expression was restricted to cells in the proliferative zone. In intestinal metaplasia, dysplasia, and GC of the intestinal and atypical subtypes, C/EBPbeta was over‐expressed ( p < 0.0001, for the association with histological type). C/EBPbeta and Ki67, a marker of cell proliferation, were also co‐expressed in primary GC. We also observed an overlap between C/EBPbeta and COX‐2 expression in GC. Using GC cell lines we show that C/EBPbeta can regulate the expression of endogenous COX‐2 and transactivate the promoter of the COX‐2 gene, depending on its methylation status. These results suggest that C/EBPbeta may be a marker of neoplastic transformation and also play an active role in gastric tumourigenesis by regulating COX‐2 expression. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.