The expression of CCAAT/enhancer binding protein (C/EBP) in the human ovary in vivo: specific increase in C/EBPβ during epithelial tumour progression

The CCAAT/enhancer binding protein (C/EBP) family of transcription factors is involved in metabolism and differentiation of cells, especially in rodent liver cells and adipocytes. Their roles in vivo and in particular during pathophysiological conditions in humans are largely unknown. We have investigated the presence of C/EBPα, -β, -δ and -ζ in normal ovaries and in epithelial ovarian tumours of different stages. Immunohistochemical experiments demonstrated that C/EBPα and C/EBPβ were preferentially expressed in epithelial/tumour cells irrespective of stage or grade of the tumour. C/EBPβ was located in the nuclei of the cells, in contrast to C/EBPα, which was present only in the cytoplasm of these cells. The nuclear localization of C/EBPβ indicates an active role of this transcription factor in tumour cells, whereas the cytoplasmic distribution suggests a more passive function of C/EBPα. C/EBPδ and -ζ demonstrated a more diverse distribution with predominant localization to epithelial cells, but stromal distribution was also noted. The intracellular distribution was confined to both the nucleus and the cytoplasm for C/EBPδ and -ζ. Western blotting demonstrated that C/EBPα, -β, -δ and -ζ were present in a majority of the samples. The amount of C/EBPβ increased markedly with malignancy, i.e. with degree of dedifferentiation, while the other members of the C/EBP family displayed a more constant expression level. These results demonstrate an association between the expression of members of the C/EBP family and the formation of epithelial ovarian tumours, with C/EBPβ as a potential marker for these tumours. As C/EBPβ is known to be expressed during proliferation of cells in vitro, it may participate in the proliferative process of ovarian epithelial tumour cells in vivo and play a central role in tumour progression. © 1999 Cancer Research Campaign