title: Expression of thioredoxin and glutaredoxin, redox-regulating proteins, in pancreatic cancer.
abstract: Pancreatic cancer (pancreatic ductal carcinoma) is one of the most malignant solid tumors with poor prognosis. There is accumulating evidence that cellular reduction/oxidation (redox) status is deeply involved in the growth promotion and drug resistance of cancer cells. We therefore investigated the expression of redox-regulating proteins, such as thioredoxin (TRX) and glutaredoxin (GRX) in surgically resected pancreatic tissues and cis-diamminedichloroplatinum (CDDP)-resistant cells. Plasma levels of TRX were also measured in subjects with pancreatic diseases. Pancreatic ductal carcinoma tissues were immunohistochemically more positive for TRX (24/32 cases) and GRX (29/32 cases) than pancreatic cystadenocarcinoma or normal pancreas tissues. Plasma levels of TRX (mean +/- SD) measured by ELISA were significantly higher in patients with pancreatic ductal carcinoma (54.8 +/- 37.6 ng/ml, n = 60) than in healthy controls (24.4 +/- 12.9 ng/ml, n = 81). CDDP-resistant subclones of HeLa cells, HeLa-CP5 cells, had higher expression of TRX (1.5 fold) and GRX (1.6 fold) compared with parental HeLa cells by immunoblotting. These results indicate the possible association of TRX and GRX with malignant potential of pancreatic ductal carcinoma.
authors.affiliation: Department of Biological Responses, Institute for Virus Research, Kyoto University, Sakyo, Japan. hnakamur@virus.kyoto-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
authors.forename: J
authors.initials: J
authors.lastname: Bai
authors.forename: Y
authors.initials: Y
authors.lastname: Nishinaka
authors.forename: S
authors.initials: S
authors.lastname: Ueda
authors.forename: T
authors.initials: T
authors.lastname: Sasada
authors.forename: G
authors.initials: G
authors.lastname: Ohshio
authors.forename: M
authors.initials: M
authors.lastname: Imamura
authors.forename: A
authors.initials: A
authors.lastname: Takabayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Yamaoka
authors.forename: J
authors.initials: J
authors.lastname: Yodoi
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000097:blood; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000473:pathology; D002945:Cisplatin / Q000494:pharmacology; D003536:Cystadenocarcinoma / Q000378:metabolism* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D004797:Enzyme-Linked Immunosorbent Assay; D054477:Glutaredoxins; D006801:Humans; D015151:Immunoblotting; D008875:Middle Aged; D010084:Oxidation-Reduction; D010088:Oxidoreductases; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D014176:Protein Biosynthesis; D013879:Thioredoxins / Q000096:biosynthesis* / Q000097:blood; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C516005:GLRX protein, human; D054477:Glutaredoxins; D013879:Thioredoxins; D010088:Oxidoreductases; D002945:Cisplatin