Hcc-2, a novel mammalian ER thioredoxin that is differentially expressed in hepatocellular carcinoma.
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.
Bioprocessing Technology Institute, #06-01, Centros, 20 Biopolis Way, Singapore 138668, Singapore.
Peter Morin
PM
Nissom
Siaw Ling
SL
Lo
Jennifer Chi Yi
JC
Lo
Peh Fern
PF
Ong
Justin Wee Eng
JW
Lim
Keli
K
Ou
Rosa Cynthia
RC
Liang
Teck Keong
TK
Seow
Maxey Ching Ming
MC
Chung
D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D016466:CHO Cells; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics; D002454:Cell Differentiation; D006224:Cricetinae; D003412:Cricetulus; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D017434:Protein Structure, Tertiary; D020543:Proteome / Q000096:biosynthesis; D040901:Proteomics / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D017423:Sequence Analysis, RNA / Q000379:methods; D017386:Sequence Homology, Amino Acid; D013879:Thioredoxins / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D020543:Proteome; D013879:Thioredoxins