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Department of Pharmacology & Toxicology, Center for Nutrient-Gene Interaction, University of Alabama at Birmingham, and Purdue University-University of Alabama at Birmingham Botanicals Center for Age-Related Disease, Birmingham, AL 35294
3To whom correspondence should be addressed. E-mail: sbarnes{at}uab.edu.
The weak estrogen-like properties of isoflavonoids were discovered over 50 y ago. In recent years, the overall effects of the isoflavones in soy on human health have been the subject of lively debate largely based on their presumed estrogenic properties. Missing from our knowledge base is the systematic identification of the cellular and biochemical targets of isoflavones and the mechanisms that they influence. Because of the benign effects of isoflavones on cellular integrity, a concentration of the isoflavones can be reached in cell culture models where almost any process can be modulated. Modern systems biology approaches and high dimensional analysis techniques offer new ways to better understand the function of how cells and integrated biological mechanisms respond to compounds such as isoflavones. Data from experiments using DNA microarray analysis for examining the effects of genistein in the developing rat uterus indicate that genistein alters the expression of 68 times as many genes as does a physiological estrogen such as 17ß-estradiol. Although these new approaches are exciting, their incipient high dimensionality places considerable strain on the quality of experimental design and meaningful statistical interpretation of the resulting data. In another approach using affinity chromatography methods, DING, a novel genistein-binding protein of yet unknown function, was isolated from human breast cancer MCF-7 cells. Its function remains to be established.
KEY WORDS: isoflavones mechanism of action DNA microarray high dimensional analysis
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