CONTRASTING PATTERNS OF REGULATION OF THE ANTIOXIDANT SELENOPROTEINS,THIOREDOXIN REDUCTASE, AND GLUTATHIONE-PEROXIDASE, IN CANCER-CELLS

There is strong evidence that selenium protects against certain human cancers, but the underlying mechanism is unknown. Glutathione peroxida se (GPX1) and thioredoxin reductase (TR), the most abundant antioxidan t selenium-containing proteins in mammals, have been implicated in thi s protection. me analyzed the expression of TR and GPX1 in the followi ng model cancer systems: (1) liver tumors in TGF alpha/c-myc transgeni c mice; (2) human prostate cell lines from normal and cancer tissues; and (3) p53-induced apoptosis in a human colon cancer cell line. TR wa s induced while GPX1 was repressed in malignancies relative to control s in transgenic mice and prostate cell Lines. In the colon cell line, p53 expression resulted in elevated GPX1, but repressed TR. The data i ndicate that TR and GPX1 are regulated in a contrasting manner in the cancer systems tested and reveal the p53-dependent regulation of selen oprotein expression. The data suggest that additional studies on selen oprotein regulation in different cancers are required to evaluate futu re implementation of selenium as a dietary supplement in individuals a t risk for developing certain cancers. (C) 1998 Academic Press.