Overexpression of CEBPβ correlates with decreased TFF1 in gastric cancer

CCAAT element binding protein beta (C/EBPβ) is an important regulator of cell growth, differentiation and in promoting tumor invasiveness. C/EBPβ is located on chromosome 20q, which is amplified in many solid tumors including gastric cancers (GC). We sought to characterize the status of C/EBPβ expression in GCs, which was recently found to repres TFF1 gene. Microarray analysis revealed overexpression of C/EBPβ in 25 of 27 (93%) GC when compared to 12 normal gastric tissue samples. RT–PCR analysis confirmed the overexpression of C/EBPβ transcripts in 54 of 59 (91%) GC. In total, 15 of 18 gastric tumors exhibited at least fivefold higher C/EBPβ transcript levels compared to their corresponding adjacent normal gastric tissue samples. Moreover, immunohistochemistry analysis demonstrated increased nuclear staining of C/EBPβ in 10 of 13 GC and at least fourfold overexpression of C/EBPβ in three primary GC compared to adjacent normal gastric tissue. Furthermore, a striking correlation of decreased TFF1 expression with increased C/EBPβ was observed in the gastric tumors studied. Microarray analysis demonstrated a loss of TFF1 expression in all 27 GC cases examined, of which 25 exhibited high C/EBPβ expression compared to normal gastric tissue. RT–PCR analysis revealed loss of TFF1 expression in 56 of 59 gastric tumors in which 54 of these tumors exhibited overexpression of C/EBPβ. Immunohistochemical analysis revealed overexpression of C/EBPβ in 10 of 13 gastric tumors that exhibited low expression of TFF1 at the protein level. Thus, overexpression of the transcription factor C/EBPβ in the majority of GCs is a novel finding.