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Detection and identification of tumor-associated protein variants in human hepatocellular carcinomas
- Source :
- Hepatology (Baltimore, Md.). 39(2)
- Publication Year :
- 2004
-
Abstract
- The proteomic approach is a valuable tool to detect and identify proteins that are associated with cancer. In previous investigations on experimentally induced rat hepatomas, we detected aldose reductase-like protein (ARLP) as a highly significant marker protein. Our present study was intended to look for the presence of similar tumor-associated marker proteins on human hepatocellular carcinomas (HCC). We found several novel tumor-associated protein variants that represent members of the aldo-keto reductase (AKR) superfamily. Human aldose reductase-like protein-1 (hARLP-1) was the most prominent tumor-associated AKR member detected in HCC by 2-dimensional electrophoresis (2-DE) and identified by mass spectrometric fingerprinting. The enzyme was found in 4 distinct forms (hARLP-1, 36/7.4 (kd/pI); hARLP-2, 36/7.2; hARLP-3, 36/6.4; and hARLP-4, 33/7.35). In addition, a human aldose reductase-like protein (hARLP-5, 36/7.6) was identified that differed from hARLP-1 by 1 amino acid (D313N), indicating 2 allelic forms of the human aldose reductase-like gene. A novel antibody directed against common parts of the hARLPs revealed hARLP reactivity in human HCC by immunohistochemistry. Furthermore, aldose reductase (AR) was identified and characterized as a tumor-associated variant. In conclusion, in all investigated human HCCs at least one of the various types of the described tumor-associated proteins of the AKR superfamily was clearly present. Of these HCC samples, 95% were positive for hARLPs as proven by 2-DE analysis and/or by use of the antibody directed against hARLP. Thus, hARLP is a strong candidate for use as an immunohistochemical diagnostic marker of human HCC.
- Subjects :
- Adult
Male
Proteomics
Carcinoma, Hepatocellular
Aldo-Keto Reductases
Biology
Reductase
Peptide Mapping
Aldehyde Reductase
medicine
Biomarkers, Tumor
Humans
Electrophoresis, Gel, Two-Dimensional
Gene
chemistry.chemical_classification
Aldose reductase
Hepatology
Liver Neoplasms
HCCS
Middle Aged
medicine.disease
Molecular biology
Immunohistochemistry
Alcohol Oxidoreductases
Biochemistry
Aldose
chemistry
Liver
Hepatocellular carcinoma
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
biology.protein
Female
Antibody
Subjects
Details
- ISSN :
- 02709139
- Volume :
- 39
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Hepatology (Baltimore, Md.)
- Accession number :
- edsair.doi.dedup.....f2257e3cc5d6397364a8825ffb6f8806