Autoantibody to thioredoxin reductase in an ovarian cancer patient.

In a patient with ovarian cancer, anti-nuclear antibodies were found by indirect immunofluorescence analysis in cultured cells. The patient's serum was used for immunoscreening of a cDNA library. Three overlapping positive clones were partial cDNA clones of thioredoxin reductase (TR), which is a member of the pyridine nucleotide-disulfide oxidoreductase family of flavoenzymes. Human autoantibodies affinity-purified with bacterial recombinant TR reacted to approximately 60-kDa polypeptide in HeLa extract in immunoblotting analysis and strongly stained around chromosome of metaphase of HeLa cells in immunofluorescence studies. Autoantibodies against recombinant TR were not found in our 100 patients with systemic autoimmune diseases. Immunoblotting analysis with bovine purified TR confirmed that the human serum had reactivities to TR. This is the first report of autoantibodies against a redox member in a cancer patient. TR has diverse functions in cell growth, death, and transformation through redox modulation with thioredoxin. Since dysregulation of TR in cancer cells is considered to be involved in some redox states of tumorigenesis, the observed antibody response in this patient could have arisen due to immunoreaction to the abnormally regulated protein.

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