Published in Cancer Detection and Prevention 2000; 24(1):53-60.

Expression of Thioredoxin and Glutaredoxin, Redox-Regulating Proteins, in Pancreatic Cancer

Hajime Nakamura1,2, Jie Bai1, Yumiko Nishinaka1, Shugo Ueda1,2, Tetsuro Sasada1, Gakuji Ohshio4, Masayuki Imamura3, Arimichi Takabayashi2, Yoshio Yamaoka2, and Junji Yodoi1

Institute for Virus Research, Kyoto University 2Department of Gastroenterological Surgery and3 Department of Surgery and Surgical Basic Science, Kyoto University Graduate School ofMedicine, 4Shiga Medical Center for Adult Disease

Address all correspondence to: Hajime Nakamura, Department of Biological Responses, Institute for Virus Research, Kyoto University, 53 Shogoin-Kawaracho, Sakyo, Kyoto 606-8397, Japan. Tel: 81-75-751-4027, Fax: 81-75-761-5766.

ABSTRACT Pancreatic cancer (pancreatic ductal carcinoma) is one of the most malignant solid tumors with poorprognosis. There is accumulating evidence that cellular reduction/oxidation (redox) status is deeply involved in thegrowth promotion and drug resistance of cancer cells. We therefore investigated the expression of redox-regulatingproteins, such as thioredoxin (TRX) and glutaredoxin (GRX) in surgically resected pancreatic tissues and cisdiamminedichloroplatinum (CDDP)-resistant cells. Plasma levels of TRX were also measured in subjects with pan-creatic diseases. Pancreatic ductal carcinoma tissues were immunohistochemically more positive for TRX (24/32cases) and GRX (29/32 cases) than pancreatic cystadenocarcinoma or normal pancreas tissues. Plasma levels ofTRX (mean &plusmin; 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 &plusmin; 12.9 ng/ml, = 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 cellsby immunoblotting. These results indicate the possible association of TRX and GRX with malignant potential ofpancreatic ductal carcinoma.

KEY WORDS: thioredoxin, glutaredoxin, pancreas, cancer, redox.

For more information, contact