Enhanced expression of mRNAs of antisecretory factor-1, gp96, DAD1 and CDC34 in human hepatocellular carcinomas

To identify differentially expressed genes in hepatocarcinogenesis, we perf ormed differential display analysis using surgically resected hepatocellula r carcinoma (HCC) and adjacent non-tumorous liver tissues. We identified fo ur cDNA fragments upregulated in HCC samples, encoding antisecretory factor -1 (AF), gp96, DAD1 and CDC34. Northern blot analysis demonstrated that the se mRNAs were expressed preferentially in HCCs compared with adjacent non-t umorous liver tissues or normal liver tissues from non-HCC patients. The ex pression of these mRNAs was increased along with the histological grading o f HCC tissues. These mRNA levels were also high in three human HCC cell lin es (HuH-7, HepG2 and HLF), irrespective of the growth state. We also demons trate that sodium butyrate, an inducer of differentiation, downregulated th e expression of AF and gp96 mRNAs, supporting in part our pathological obse rvation. Immunohistochemical analysis revealed that gp96 and CDC34 proteins were preferentially accumulated in cytoplasm and nuclei of HCC cells, resp ectively. Overexpression of these genes could be an important manifestation of HCC phenotypes and should provide clues to understand the molecular bas is of hepatocellular carcinogenesis. (C) 2001 Elsevier Science B.V. All rig hts reserved.