Chemopreventive Action of Human Selenium Binding Protein

Beth Israel Deaconess Medical Center, Boston MA

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Abstract

DESCRIPTION (provided by applicant): The chemopreventive (anti-cancer) action of selenium is becoming increasingly recognized in both experimental animals and in the general human population. However, the mechanism(s) through which selenium exerts this effect is (are) far from certain. Using a novel method designed to isolate genes expressed differentially between two cell types, we have identified thirteen genes expressed preferentially or exclusively by the slowly growing, androgen-sensitive LNCaP human prostate cancer cells or by the more rapidly growing, androgen-insensitive PC3 human prostate cancer cells. One of these genes, designated hSP56, encodes the human homolog of a mouse gene, the product of which is a selenium binding protein that has been proposed as a mediator of selenium's growth inhibitory effect in vitro and chemopreventive effect in vivo. We have discovered that hSP56 is expressed by LNCaP but not by PC-3 and that its expression is reversibly downregulated by androgen. Moreover, artificial downregulation of hSP56 expression by antisense oligodeoxynucleotides mimics the mitogenic effect of androgen. We hypothesize that hSP56 protein may play a role in the prostate cancer phenotype and in the chemopreventive effects of selenium in prostate and other cancers. To begin to test this hypothesis: 1) we will investigate the cellular and molecular properties of hSP56 protein including its binding of selenium, and 2) we will elucidate the role of hSP56 in the prostate cancer phenotype in vitro using gain-of-function and loss-of-function approaches. This work will provide essential data leading to new ideas in prostate cancer biology and the role of selenium in cancer prevention.