The prevalence of activated ras oncogenes in human primary tumors suggests a central role for this oncogene in the initiation and progression of human cancer. Melittin, a 26 amino acid, amphipathic peptide from bee venom, has the ability to suppress the transforming effects of the ras oncogene in cultured mammalian cells. The long term objectives of the studies outlined in this proposal are to gain a better understanding of the mechanism by which melittin is able to suppress ras oncogene mediated cellular transformation. Experiments outlined in this proposal will analyze the structural features of melittin that enable melittin to perform this activity. In addition, the ability of melittin to counter-select for transformation by human tumor cells harboring different activated ras oncogene (Harvey, Kirstein & N-ras) will be investigated. The biochemical basis of melittin mediated suppression of transformation by the ras oncogene will also be examined. It is hoped that understanding the mechanism by which melittin suppresses ras mediated cellular transformation will provide insight into the mechanism of action of the ras oncogene and may provide novel avenues for anti-cancer therapy.
