|Barrett, J Carl|
|Wang, Thomas - Tom|
Submitted to: Breast Cancer Research and Treatment
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/17/2007
Publication Date: 8/9/2007
Citation: Lavigne, J.A., Takahashi, Y., Chandramouli, G.V., Liu, H., Shih, J., Perkins, S.N., Hursting, S.D., Barrett, J., Wang, T.T. 2007. Concentration-dependent effects of genistein on global gene expression in MCF-7 breast cancer cells: an oligo microarray study. Breast Cancer Research and Treatment. [DOI 10.1007/s10549-007-9705-6]. Interpretive Summary: Many studies have correlated the consumption of soy-rich diets with a decreased risk of developing hormone-dependent cancers, including breast cancer. Genistein is a candidate breast cancer-preventive phytochemical found at high levels in soybeans and soy foods. To better understand how genistein provides beneficial effects on breast cancer prevention, we utilized a global gene analysis approach to examine the effects of genistein, at doses in the physiologic range, on global gene expression patterns in an estrogen-dependent breast cancer cell culture model. We found that genistein altered the expression of genes belonging to a wide range of pathways, including the female sex hormone and DNA repair-related pathways. At low concentration, genistein-activated genes are involved in the growth of breast cancer cells. At high a concentration, genistein up-regulated genes activate cell death and inhibit cell growth. These findings provide evidence for a molecular signature of genistein's effects in breast cancer cells and lay the foundation for elucidating the mechanisms of genistein's biological impact in breast cancer cells. This work provides novel information for a cancer research scientist regarding molecular targets and mechanisms of the action of soy-derived phytochemicals and will serve as important bases for future design of cancer preventive strategy.
Technical Abstract: Breast cancer is the most commonly diagnosed cancer among U.S. women; there is great interest in developing preventive and treatment strategies for this disease. Because breast cancer incidence is much lower in countries where women consume high levels of soy, compounds in this food source have been studied for their effects on breast cancer. Genistein, found at high levels in soybean and soy foods, is a controversial candidate for a breast cancer preventive phytochemical whose effects on breast cells are complex. To understand more clearly the molecular mechanisms underlying the effects of genistein on breast cancer cells, we used a DNA microarray approach to examine the global gene expression patterns in MCF-7 breast cancer cells at both physiologic (1 or 5 microM) and pharmacologic (25 microM) genistein concentrations. Microarray analyses were performed on vehicle-treated MCF-7 cells along with those exposed for 48 hours to these 3 different genistein concentrations. We found that genistein altered the expression of genes belonging to a wide range of pathways, including estrogen- and p53-mediated pathways. At 1 and 5 microM, genistein elicited an expression pattern that likely contributes to an overall increase in cell proliferation, confirming what has been observed in cultured MCF-7 cells, while at 25 microM, genistein effected a pattern that likely contributes to increased apoptosis, decreased proliferation, and decreased total cell number, also confirming cell culture results. These findings provide evidence for a molecular signature of genistein's effects in MCF-7 cells and lay the foundation for elucidating the mechanisms of genistein's biological impact on breast cancer cells.