In this revised application the investigators plan their studies focusing on the response that alpha-feto protein/E2 (AFP/E2) elicits in estrogen-dependent breast cancer tissue. The investigators state that AFP is a prohormone. A biologically active product of unknown structure designated as AFP/E2 is generated in vitro when purified rodent or human AFP is incubated with estradiol (E2) for one hour at room temperature. They hypothesize that AFP/E2 delivers a signal to the cell (probably via a membrane receptor) that attenuates or shuts down the biochemical process through which the estrogen response is enabled.
Specific aims are to determine the chemical nature of """"""""AFP/E2"""""""" and to determine where it interferes in the biochemical mechanism of estrogen response. They plan also to assess the relevance of this novel growth-inhibitory activity of AFP/E2 by testing its effect against freshly resected human breast cancers growing as first transplant generation xenografts under the kidney capsule of immunosuppressed mice. The investigators anticipate that this project will substantially augment knowledge of this heretofore unknown control on endocrine cancer and possible uncover new strategies for the prevention and/or treatment of breast cancer.
|Bennett, J A; Semeniuk, D J; Jacobson, H I et al. (1997) Similarity between natural and recombinant human alpha-fetoprotein as inhibitors of estrogen-dependent breast cancer growth. Breast Cancer Res Treat 45:169-79|
|Allen, S H; Bennett, J A; Mizejewski, G J et al. (1993) Purification of alpha-fetoprotein from human cord serum with demonstration of its antiestrogenic activity. Biochim Biophys Acta 1202:135-42|