Increased expression of specific thioredoxin family proteins; a pilot immunohistochemical study on human hepatocellular carcinoma

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Cunnea, P.Department of Biosciences and Nutrition at NOVUM, Karolinska Institutet, Stockholm, Sweden (author)

Hepatocellular Carcinoma (HCC) is one of the most frequent cancers worldwide, however, prognosis remains poor following its discovery. We investigate the Thioredoxin superfamily of proteins as diagnostic markers for HCC. Furthermore, we delineate possible roles of the endoplasmic reticulum member of the superfamily, ERdj5, in carcinogenesis. Using antibodies against Thioredoxin 1, Thioredoxin Reductase 1 and ERdj5, we performed immunohistochemistry on paraffin embedded liver biopsy sections from HCC patients. All three redox proteins exhibited elevated expression levels in tumor tissue compared to internal control, with ERdj5 showing a remarkable 3-fold increase. In vitro cell viability experiments using Hepatocellular Carcinoma HuH7 cells treated with ERdj5 small interfering RNA showed that ERdj5 knockdown cells exhibited less resistance to Doxorubicin (chemotherapy drug), but more resistance to Tunicamycin (Endoplasmic Stress inducer), compared to control cells. In conclusion, we introduce members of the Thioredoxin superfamily as possible immunohistochemical markers in the diagnostics of hepatocellular carcinoma and indicate a potential defensive role for ERdj5 in chemotherapeutic drug resistance.

Fernandes, APKarolinska Institutet (author)
Capitanio, A.Department of Laboratory Medicine, Pathology Division, Karolinska University Hospital, Huddinge, Stockholm, Sweden (author)
Eken, S.Department of Laboratory Medicine, Pathology Division, Karolinska University Hospital, Huddinge, Stockholm, Sweden (author)
Spyrou, GiannisDepartment of Biosciences and Nutrition at NOVUM, Karolinska Institutet, Stockholm / Foundation for Biomedical Research, Academy of Athens, Athens, Greece(Swepub:liu)ioasp42 (author)
Björnstedt, M.Karolinska Institutet (author)
Karolinska InstitutetDepartment of Biosciences and Nutrition at NOVUM, Karolinska Institutet, Stockholm, Sweden (creator_code:org_t)

In:International journal of immunopathology and pharmacology: Biolife20:1, s. 17-240394-63202058-7384

By the author/editor: Cunnea, P.; Fernandes, AP; Capitanio, A.; Eken, S.; Spyrou, Giannis; Björnstedt, M.

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