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

Abstract

To identify differentially expressed genes in hepatocarcinogenesis, we performed differential display analysis using surgically resected hepatocellular carcinoma (HCC) and adjacent non-tumorous liver tissues. We identified four cDNA fragments upregulated in HCC samples, encoding antisecretory factor-1 (AF), gp96, DAD1 and CDC34. Northern blot analysis demonstrated that these mRNAs were expressed preferentially in HCCs compared with adjacent non-tumorous liver tissues or normal liver tissues from non-HCC patients. The expression of these mRNAs was increased along with the histological grading of HCC tissues. These mRNA levels were also high in three human HCC cell lines (HuH-7, HepG2 and HLF), irrespective of the growth state. We also demonstrate that sodium butyrate, an inducer of differentiation, downregulated the expression of AF and gp96 mRNAs, supporting in part our pathological observation. Immunohistochemical analysis revealed that gp96 and CDC34 proteins were preferentially accumulated in cytoplasm and nuclei of HCC cells, respectively. Overexpression of these genes could be an important manifestation of HCC phenotypes and should provide clues to understand the molecular basis of hepatocellular carcinogenesis.

Blockade of ubiquitin-conjugating enzyme CDC34 enhances anti-myeloma activity of Bortezomib/Proteasome inhibitor PS-341

“…These findings are consistent with a previous study suggesting that CDC34 is upregulated in malignant versus normal plasma cells (De Vos et al, 2002). Moreover, higher levels of CDC34 transcripts have also been reported in acute lymphoblastic leukemia and hepatocellular carcinomas (Tanaka et al, 2001). Together, these findings suggest that CDC34 may regulate the growth of tumor cells.…”

“…A recent report showed a high expression of CDC34 in pediatric T-cell acute lymphoblastic leukemia (Eliseeva et al, 2001) and hepatocellular carcinoma (Tanaka et al, 2001); however, the mechanism regulating CDC34 in cancer cells has not been characterized.…”

Comparison of gene expression profiling between malignant and normal plasma cells with oligonucleotide arrays

“…Of note, this gene has already been reported to be upregulated in acute lymphoblastic leukemia and hepatocellular carcinomas (Tanaka et al, 2001). CDC34 is a ubiquitin-conjugating enzyme that appears to play a particularly important role in the control of the cell cycle in budding yeast and Xenopus (Michael and Newport, 1998).…”

Significant correlation between expression level of HSP gp96 and progression of hepatitis B virus induced diseases

“…We previously reported the identification of an HBV-specific HLA class I specific peptide bound to gp96 in HCC patients [17,18] , indicating its possible roles in immunity of HBV-induced HCC patients. At the same time, a Japanese group showed that gp96 expression level in HCC patients increased [19] and implied its effect on tumorigenicity. It is estimated that 350-400 million people worldwide are persistently infected with HBV and some of these persistent infected patients develop into cirrhosis or HCC in later stage [20,21] .…”