A Role For Selenoproteins In Prostate Cancer Prevention

There is considerable effort focused on investigating the potential of selenium in the prevention of prostate cancer. To study whether selenoprotein (SP) levels might affect disease progression, an animal model was developed in which mice express reduced levels of SP due to the presence of a mutant Sec tRNA, and an increased risk for prostate cancer due to the expression of an oncogene in that organ. Reduction of SP levels resulted in the accelerated appearance of histopathological features associated with prostate cancer in these mice. Studies were conducted to investigate how lower SP levels might contribute to cancer development. The SP deficient animals were irradiated and lymphocytes obtained were shown to be more prone to DNA damage when measured by micronuclei formation following irradiation, as compared to control animals. In order to investigate whether one particular SP may be responsible for this observation, LNCaP human prostate cancer cells were engineered to either over-express or under-express GPx-1. These cells were used to investigate the relationship between susceptibility of radiation-induced DNA damage and GPx-1 levels and an inverse association was indicated by examining micronuclei formation. These data implicate SP in prostate cancer etiology and perhaps the mechanism of protection by selenium. This work is supported by NIH grant # RO1 CA101053-01 to AMD.