Expression of thioredoxin and glutaredoxin, redox-regulating proteins, in pancreatic cancer

Pancreatic cancer (pancreatic ductal carcinoma) is one of the most malignan t solid tumors with poor prognosis. There is accumulating evidence that cel lular reduction/oxidation (redox) status is deeply involved in the growth p romotion and drug resistance of cancer cells. We therefore investigated the expression of redoxregulating proteins, such as thioredoxin (TRX) and glut aredoxin (GRX) in surgically resected pancreatic tissues and cis-diamminedi chloroplatinum (CDDP)-resistant cells. Plasma levels of TRX were also measu red in subjects with pancreatic diseases. Pancreatic ductal carcinoma tissu es 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 hi gher 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 immunoblotti ng. These results indicate the possible association of TRX and GRX with mal ignant potential of pancreatic ductal carcinoma.