Decreased Expression of the CCAAT/enhancer Binding Protein Alpha Gene Involved in Hepatocyte Proliferation in Human Hepatocellular Carcinomas

CCAAT/enhancer binding protein alpha (C/EBPalpha), expressed at a high level in liver, plays an important role in proliferation and differentiation of hepatocytes. Previous studies showed that an expression level of the C/EBPalpha gene in hepatocytes was downregulated in response to proliferation signals and that forced expression of the C/EBPalpha gene in a number of cells caused cell cycle arrest. We compared the expression level of the C/EBPalpha gene in surgical specimens between hepatocellular carcinoma and non-tumorous regions of the same patients. In 9 out of 13 cases, the expression level in the tumors was decreased compared with that in corresponding non-tumorous regions. Transfection of the C/EBPalpha gene into C/EBPalpha-negative human hepatocellular carcinoma HLF cells, however, did not influence the rate of cell proliferation or cell cycle. Our present data suggest that the expression of the C/EBPalpha gene was downregulated in the majority of human hepatocellular carcinoma but the expression may not be directly associated with impaired proliferative activity of hepatocellular carcinoma cells.