Regulatory role of CCAAT/enhancer binding protein-beta in the production of plasma proteins in yolk sac tumor.

Yolk sac tumor (endodermal sinus tumor) is a malignant germ cell tumor characterized by AFP production, in which histologic foci similar to hepatocellular carcinoma occasionally coexist. We assumed a possible contribution of CCAAT/enhancer binding protein (C/EBP)-beta, a transcription factor implicated in the regulation of plasma proteins in the liver, to the regulation of AFP production and to the expression of other plasma proteins in yolk sac tumor cells because our immunohistochemical analysis revealed nuclear expression of C/EBP-beta in human yolk sac tumors. Overexpression of C/EBP-beta in a rat yolk sac tumor cell line, AT-2-TC, increased production of AFP and other plasma proteins, including albumin, alpha-1-antitrypsin, hepatoglobin, and transferrin. Liver-enriched transcription factors, including hepatocyte nuclear factors (HNF)-1alpha, -1 beta, and -4, were also induced. The induction of this protein expression was only evident in xenografts, where C/EBP-beta was phosphorylated and the activating isoform of C/EBP-beta was relatively predominant. These results indicate that C/EBP-beta plays a role in the production of plasma proteins of yolk sac tumors.