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/EBP alpha, -beta, -delta and -zeta in normal ovaries and in epithelial ovarian tumours of different stages. Immunohistochemical experiments demonstrated that C/EBP alpha and C/EBP beta were preferentially expressed in epithelial/tumour cells irrespective or stage or grade of the tumour. C/EBP beta was located in the nuclei of the cells. in contrast to C/EBP alpha, which was present only in the cytoplasm of these cells. The nuclear localization of C/EBP beta indicates an active role of this transcription factor in tumour cells. whereas the cytoplasmic distribution suggests a more passive function of C/EBP alpha. C/EBP delta and -zeta 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/EBP delta and -zeta. Western blotting demonstrated that C/EBP alpha, -beta, -delta and -zeta were present in a majority of the samples. The amount of C/EBP beta 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/EBP beta as a potential marker for these tumours. As C/EBP beta 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.