Increased expression of the transcription factors CCAAT-enhancer binding protein-beta (C/EB beta) and C/EBP zeta (CHOP) correlate with invasiveness of human colorectal cancer

Regulation of cell differentiation is most often impaired in malignant tumo rs and may represent a key mechanism for the progression of the disease. CC AAT-enhancer binding protein (C/EBP) is a family of transcription factors i nvolved in the regulation of embryonic gut development in rodents, which ha s also been detected in various malignancies, e.g., liposarcomas and breast and ovarian epithelial tumors. We studied the relationship between C/EBP a nd tumor histology (Duke's invasive stage and pathological grade) in colore ctal cancer. Immunoblotting techniques were used on microdissected fresh fr ozen tumor specimens, and expression of C/EBP alpha, C/EBP beta and C/EBP z eta (CHOP) was analyzed in addition to that of the cell-cycle regulator p53 and the proliferation marker PCNA. Expression of C/EBP beta (LAP isoforms) was markedly increased in all tumors compared with normal colon mucosa, Al though the inter-patient variability was large, we found that LIP, the isof orm of C/EBP beta known to inhibit transcription, was expressed at higher l evels in Duke's stage B tumors compared with Duke's stage A, whereas Duke's C tumors had the lowest LIP expression. A similar relationship was seen fo r CHOP, The cell-cycle regulator gene p53 was the only factor that clearly correlated with pathological grade: a decrease in p53 expression was demons trated, Our data suggest that genetic and cellular events involving C/EBP b eta and CHOP are important for tumor invasion and that these events do not appear to be related to the pathological grade of the tumor. Int. J, Cancer 86:337-343, 2000, (C) 2000 Wiley-Liss, Inc.