Hcc‐2, a novel mammalian ER thioredoxin that is differentially expressed in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver. Thus there is great interest to identify novel HCC diagnostic markers for early detection of the disease and tumour specific associated proteins as potential therapeutic targets in the treatment of HCC. Currently, we are screening for early biomarkers as well as studying the development of HCC by identifying the differentially expressed proteins of HCC tissues during different stages of disease progression. We have isolated, by reverse transcriptase and polymerase chain reaction (RT-PCR), a 1741 bp cDNA encoding a protein that is differentially expressed in HCC. This novel protein was initially identified by proteome analysis and we designate it as Hcc-2. The protein is upregulated in poorlydifferentiated HCC but unchanged in well-differentiated HCC. The full-length transcript encodes a protein of 363 amino acids that has three thioredoxin (Trx) (CGHC) domains and an ER retention signal motif (KDEL). Fluorescence GFP tagging to this protein confirmed that it is localized predominantly to the cytoplasm when expressed in mammalian cells. Protein alignment analysis shows that it is a variant of the TXNDC5 gene, and the human variants found in Genbank all show close similarity in protein sequence. Functionally, it exhibits the anticipated reductase activity in the insulin disulfide reduction assay, but its other biological role in cell function remains to be elucidated. This work demonstrates that an integrated proteomics and genomics approach can be a very powerful means of discovering potential diagnostic and therapeutic protein targets for cancer therapy.

The influence of TXNDC5 gene on gastric cancer cell

“…Wang et al (2007) has suggested that an upregulation of TXNDC5 could be involved in the early development of colorectal cancer by proteomic analysis of differentially expressed proteins in adenoma, when compared with matched normal mucosa and cancer tissue. Nissom et al (2006) has found that the TXNDC5 expression is upregulated in poorly differentiated hepatic carcinoma (HCC), but unchanged in well-differentiated HCC and thought the gene could play some roles in tumor progression. Claudio et al (2002) has found that TXNDC5 is upregulated in multiple myeloma and Wei et al (2007) showed that TXNDC5 is upregulated in androgen-independent prostate cancer.…”

Proteomic identification of down-regulation of oncoprotein DJ-1 and proteasome activator subunit 1 in hepatitis B virus-infected well-differentiated hepatocellular carcinoma

“…α-enolase was strongly expressed in G3 tumours compared with G1 and G2 tumours (12), and glutamine synthetase was highly expressed in HCV-infected G1 tumours (15). Recently, protein Hcc-2 was found to be upregulated in G3 tumours but unchanged in G1 tumours (16). In addition, proteome profiles of HCC are also virus-dependent.…”

Contribution of oncoproteomics to cancer biomarker discovery

“…This novel protein was identified by proteomic analysis and was designated as Hcc-2, which is up-regulated in poor-differentiated HCC but unchanged in well-differentiated HCC. This work demonstrated that an integrated proteomic and genomic approach could be a very powerful means of discovering potential diagnostic and therapeutic protein targets for cancer therapy [51]. …”