Lunasin, a novel and promising chemopreventive compound isolated from soybean cotyledon, is a 43-amino acid peptide that contains a -RGD-cell adhesion motif followed by 8 aspartic acid residues at the carboxyl end and a structurally conserved helix region. We showed previously that lunasin peptide applied exogenously reduces foci formation in mouse fibroblast cells treated with chemical carcinogens and inhibits skin tumorigenesis induced by chemical carcinogens in mice when applied topically. In this study, lunasin peptide applied to cell culture suppresses foci formation in E1A-transfected mouse fibroblast NIH 3T3 cells. Within 18 h of exogenous application, lunasin internalizes into the cell and localizes in the nucleus. In an initial study of genes affected by lunasin, the peptide increases p21 protein levels fivefold in cells transfected with E1A but not in untransfected cells. In contrast to its inhibitory effects on cell transformation, lunasin has no effect on growth of imicroMortalized (nontumorigenc) and established cancer cells. This is the first report that lunasin suppresses transformation of mamicroMalian cells induced by an oncogene (E1A) in addition to chemical carcinogens.