Glucocorticoids Control β-Catenin Protein Expression and Localization through Distinct Pathways that Can Be Uncoupled by Disruption of Signaling Events Required for Tight Junction Formation in Rat Mammary Epithelial Tumor Cells

In Con8 rat mammary epithelial tumor cells, the synthetic glucocorticoid dexamethasone stimulates the remodeling of tight junctions and adherens junctions before formation of highly sealed tight junctions. In this study, the expression and localization of key components of the apical junction were examined as potential targets of glucocorticoid signaling. Western blot and RT-PCR demonstrated that dexamethasone up-regulated β-catenin protein and transcript expression and nearly ablated β-catenin phosphorylation under conditions that led to a significant increase in monolayer transepithelial resistance. Indirect immunofluorescence revealed that dexamethasone treatment also caused β-catenin to localize predominantly at the cell membrane rather than the nucleus. The glucocorticoid regulation of β-catenin expression and localization was not a consequence of dexamethasone inhibition of cell growth, because both responses were unaltered in the presence of hydroxyurea. The steroid induction of β-catenin expressio...