Abstract
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.
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Acknowledgements
This work was supported by grant awards from the National Cancer Institute: CA67900 (SM Powell). The contents of this work are solely our responsibility, and do not necessarily represent the official views of the NCI or the University of Virginia. We also thank Jeffrey Harper for technical help.
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Sankpal, N., Moskaluk, C., Hampton, G. et al. Overexpression of CEBPβ correlates with decreased TFF1 in gastric cancer. Oncogene 25, 643–649 (2006). https://doi.org/10.1038/sj.onc.1209081
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DOI: https://doi.org/10.1038/sj.onc.1209081
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