1. Hcc-2, a novel mammalian ER thioredoxin that is differentially expressed in hepatocellular carcinoma.
- Author
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Nissom PM, Lo SL, Lo JC, Ong PF, Lim JW, Ou K, Liang RC, Seow TK, and Chung MC
- Subjects
- Amino Acid Motifs genetics, Amino Acid Sequence, Animals, Biomarkers, Tumor genetics, CHO Cells, Carcinoma, Hepatocellular diagnosis, Carcinoma, Hepatocellular genetics, Cell Differentiation, Cricetinae, Cricetulus, Endoplasmic Reticulum enzymology, Endoplasmic Reticulum genetics, Gene Expression Profiling methods, Humans, Liver Neoplasms diagnosis, Liver Neoplasms genetics, Molecular Sequence Data, Neoplasm Proteins genetics, Protein Structure, Tertiary, Proteome biosynthesis, Proteomics methods, Reverse Transcriptase Polymerase Chain Reaction methods, Sequence Analysis, RNA methods, Sequence Homology, Amino Acid, Thioredoxins genetics, Up-Regulation, Biomarkers, Tumor biosynthesis, Carcinoma, Hepatocellular enzymology, Gene Expression Regulation, Neoplastic, Liver Neoplasms enzymology, Neoplasm Proteins biosynthesis, Thioredoxins biosynthesis
- 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 1741bp 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 poorly-differentiated 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.
- Published
- 2006
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