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.
Regalo
G
G
IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal.
Canedo
P
P
Suriano
G
G
Resende
C
C
Campos
M L
ML
Oliveira
M J
MJ
Figueiredo
C
C
Rodrigues-Pereira
P
P
Blin
N
N
Seruca
R
R
Carneiro
F
F
Machado
J C
JC
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics*; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000235:genetics*; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008679:Metaplasia / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D022782:CCAAT-Enhancer-Binding Protein-beta; D019394:Ki-67 Antigen; D051546:Cyclooxygenase 2