Considerable animal and human data have indicated that selenium is effective in 
reducing the incidence of several different types of cancer, including that of 
the prostate. However, the mechanism by which selenium inhibits carcinogenesis 
remains unknown. One possibility is that dietary selenium influences the levels 
of selenium-containing proteins, or selenoproteins. Selenoproteins contain 
selenium in the form of selenocysteine and perform a variety of cellular 
functions, including antioxidant defense. To determine whether the levels of 
selenoproteins can influence carcinogenesis independent of selenium intake, a 
unique mouse model was developed by breeding two transgenic animals: mice with 
reduced selenoprotein levels because of the expression of an altered 
selenocysteine-tRNA (i6A-) and mice that develop prostate cancer because of the 
targeted expression of the SV40 large T and small t oncogenes to that organ 
[C3(1)/Tag]. The resulting bigenic animals (i6A-/Tag) and control WT/Tag mice 
were assessed for the presence, degree, and progression of prostatic epithelial 
hyperplasia and nuclear atypia. The selenoprotein-deficient mice exhibited 
accelerated development of lesions associated with prostate cancer progression, 
implicating selenoproteins in cancer risk and development and raising the 
possibility that selenium prevents cancer by modulating the levels of these 
selenoproteins.