The expression of CCAAT/enhancer binding protein (C/EBP) in the human ovary in vivo: specific increase in C/EBP beta 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 roden t liver cells and adipocytes. Their roles in vivo and in particular during pathophysiological conditions in humans are largely unknown. We have invest igated the presence of C/EBP alpha, -beta, -delta and -zeta in normal ovari es and in epithelial ovarian tumours of different stages. Immunohistochemic al experiments demonstrated that C/EBP alpha and C/EBP beta were preferenti ally 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. Th e nuclear localization of C/EBP beta indicates an active role of this trans cription factor in tumour cells. whereas the cytoplasmic distribution sugge sts a more passive function of C/EBP alpha. C/EBP delta and -zeta demonstra ted a more diverse distribution with predominant localization to epithelial cells, but stromal distribution was also noted. The intracellular distribu tion 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 in creased markedly with malignancy, i.e. with degree of dedifferentiation, wh ile the other members of the C/EBP family displayed a more constant express ion level. These results demonstrate an association between the expression of members of the C/EBP family and the formation of epithelial ovarian tumo urs, 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 pa rticipate in the proliferative process of ovarian epithelial tumour cells i n vivo and play a central role in tumour progression.