|De Lumen, Ben|
Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract Only
Publication Acceptance Date: 1/31/2008
Publication Date: 4/9/2008
Citation: Su, Y., De Lumen, B., Simmen, R.C. 2008. Soy components genistein and lunasin regulate E-cadherin and Wnt signaling in mammary epithelial cells [abstract]. The FASEB Journal. 22:700.1.
Interpretive Summary: The linkage between nutrition and cancer prevention has been widely studied. In our lab, we have shown lifetime consumption of soy diet is also protective in rat carcinogen-induced breast cancer model. Soy dietary components genistein and lunasin have been shown as cancer chemoprevention agents by others. In present study, we found that genistein inhibited basal or stimulated proliferation. Genistein, but not lunasin, can enhance cell adhesion complex formation to maintain epithelial cell morphology.
Technical Abstract: Enhanced Wnt/beta-catenin signaling and loss of E-cadherin expression are considered hallmarks of tumorigenesis. We previously showed by microarray gene profiling that dietary intake of soy-based AIN-93G diets altered components of Wnt/beta-catenin signaling in rat mammary epithelial cells. To further evaluate the molecular effectors, biological consequence, and mechanism(s) underlying dietary soy effects, we utilized the mouse mammary epithelial cell line HC11 treated with the soy isoflavone genistein and the soy peptide lunasin at physiologically relevant doses. Genistein (40 nM) inhibited basal and wnt1-activated cell proliferation after 7 days of treatment. Further, genistein increased beta-catenin and E-cadherin protein levels and formation of membrane E-cadherin/ beta-catenin complexes. Lunasin (1 micro M) induced E-cadherin gene and protein expression, but had no effect on membrane E-cadherin/ beta-catenin complex formation. Cells treated with Wnt1 (50ng/ml) had increased nuclear beta-catenin localization and expression of its target genes cyclin D1 and c-myc, relative to the controls. Genistein completely abolished Wnt1 mediated induction of these genes. Results implicate genistein and lunasin in the regulation of E-cadherin and wnt/beta-catenin signaling in mammary epithelial cells, and provide a mechanism by which dietary soy protects against mammary tumors.