Soy Components Genistein And Lunasin Regulate E‐Cadherin And Wnt Signaling In Mammary Epithelial Cells

Abstract

Enhanced Wnt/β‐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/β‐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 β‐catenin and E‐cadherin protein levels and formation of membrane E‐cadherin/β‐catenin complexes. Lunasin (1 μM) induced E‐cadherin gene and protein expression, but had no effect on membrane E‐cadherin/β‐catenin complex formation. Cells treated with Wnt1(10ng/ml) had increased nuclear β‐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/β‐catenin signaling in mammary epithelial cells, and provide a mechanism by which dietary soy protects against mammary tumors.