Transforming Growth Factor-α Abrogates Glucocorticoid-stimulated Tight Junction Formation and Growth Suppression in Rat Mammary Epithelial Tumor Cells

摘要: Abstract The glucocorticoid and transforming growth factor-α (TGF-α) regulation of cell-cell contact was investigated in the Con8 mammary epithelial tumor cell line derived from a 7,12-dimethylbenz(α)anthracene-induced rat adenocarcinoma. In monolayers cultured on permeable filter supports, synthetic glucocorticoid, dexamethasone, coordinately suppressed [3H]thymidine incorporation, stimulated monolayer transepithelial electrical resistance (TER), decreased paracellular leakage [3H]inulin or [14C]mannitol across monolayer. These processes dose dependently correlated with receptor occupancy function. Constitutive production TGF-α transfected cells exogenous treatment prevented suppression response disrupted tight junction formation without affecting responsiveness. Treatment hydroxyurea araC demonstrated that de novo DNA synthesis is not requirement for factor disruption junctions. Immunofluorescence analysis revealed ZO-1 protein localized exclusively at periphery dexamethasone-treated caused to relocalize back cytoplasmic compartment. Taken together, our results demonstrate glucocorticoids can regulate inhibition TGF-α, override both effects glucocorticoids. have uncovered novel functional “cross-talk” between which potentially regulates proliferation differentiation cells.