Soy has clearly been a functional food in the spotlight during the 1990's (Kuhn, 1996). In addition to being a high quality protein, soy is now known to play a preventive and/or therapeutic role in a number of chronic diseases, including heart disease, osteoporosis and cancer (Messina, Messina and Setchell, 1994).
Several classes of anticarcinogens have been identified in soybeans, including protease inhibitors, phytosterols, saponins, phenolic acids, phytic acid, and isoflavones (Messina and Barnes, 1991). Of these, isoflavones (genistein and daidzein) are particularly noteworthy because soybeans are the only significant dietary source of these compounds (Anderson and Garner, 1997). Isoflavones are heterocyclic phenols structurally similar to the estrogenic steroids, and thus have been shown to possess both estrogenic and antiestrogenic activity. Because they are weak estrogens, isoflavones may act as anti-estrogens by competing with the more potent, naturally-occurring endogenous estrogens (e.g., 17B-estradiol) for binding to the estrogen receptor (ER). This has important implications for reducing breast cancer risk. While not all studies agree (Messina, Barnes and Setchell, 1997), epidemiologic evidence indicates that women in Southeast Asian populations that consume diets containing high amounts of soy (10-50 grams/day) have a four- to six-fold decreased risk of breast cancer compared to American women, who routinely consume negligible amounts of this legume (1-3 grams/day).
There are several stages in the development of breast cancer in which soy could alter the outcome for breast cancer. However, there has been little research conducted to evaluate dietary factors that alter the progression of this disease in animal models that mimic the physiological state observed in post-menopausal women with estrogen-dependent tumors. In the past few decades, health professionals have developed dietary recommendations for the reduction of some symptoms associated with coronary heart disease. There have been no attempts to establish dietary recommendations for post-menopausal women with estrogen-dependent breast cancer.
a. Characterize the effects of the phytoestrogens in gene regulation by the two forms of the estrogen receptor, ERa and ERß.
b. Determine dose response profiles for ERa and ERß for phytoestrogens using concentration ranges based on available competitive binding data.
c. Determine the effects of expression of co-regulators on the activities of soy phytoestrogens.
d. Assess whether phytoestrogens alter the level of expression of co-regulators in cell lines and in vivo.
e. To determine wheter a diet rich in soybean components can prevent or delay development of prostate enlargement or mammary tumors in a novel transgenic model of these diseases--the MT-hGH mouse.
