Alphafetoprotein (AFP) and synthetic peptide derivatives are potent antiestrotrophic agents with significant potential as a novel class of therapeutic agents against breast cancer. The activity of the full-length protein is localized within an eight amino acid peptide derived from the native human alphafetoprotein elevating this synthetic peptide to a primary target for development. AFP peptide blocks the estrogen-stimulated growth of normal and neoplastic tissues. The anti-oncotic activity of AFP and its derivative peptides is unique to estrogen receptor-containing cells in vivo and in vitro. Until recently, much effort has been invested into the study of the antiestrotrophic activity of AFP fragments and peptides, with the focus on identification of the protein active site, yet very little is known about the cellular mechanism of AFP peptide action. The goal of this project is to discover the fundamental molecular mechanism(s) of AFP peptide activity. To accomplish this goal, it is necessary to identify the components of the cellular machinery involved in AFP action so that we may understand the biochemical and molecular basis of AFP peptide activity. The result of this work is expected to contribute to the development of novel therapeutic targets and will provide valuable information concerning the potential of AFP peptides as agents in the prevention, treatment, and diagnosis of breast cancer.
