GLUCOCORTICOID-INDUCED FUNCTIONAL POLARITY OF GROWTH-FACTOR RESPONSIVENESS REGULATES TIGHT JUNCTION DYNAMICS IN TRANSFORMED MAMMARY EPITHELIAL TUMOR-CELLS

The synthetic glucocorticoid, dexamethasone, induces the ''normal-like '' differentiated property of tight junction formation and suppresses growth of the Con8 mammary epithelial tumor cell line, derived from a 7,12-dimethylbenz(alpha)anthracene-induced rat mammary adenocarcinoma. Characterization of the transepithelial electrical resistance of Con8 mammary tumor cells cultured on permeable supports revealed that a no vel response to dexamethasone is the generation of a polarized cell mo nolayer with respect to epidermal growth factor receptor responsivenes s, Administration of transforming growth factor-alpha (TGF-alpha) to t he basolateral, but not the apical, plasma membrane compartment disrup ted the glucocorticoid-stimulated tight junction barrier, Confocal imm unofluorescence microscopy revealed that dexamethasone caused the ZO-1 tight junction-associated protein to localize exclusively to the apic al border of laterally adjacent membranes of the cell periphery, where as basolateral administration of TGF-alpha caused the redistribution o f ZO-1 back to disorganized aggregates along the cell periphery, In co ntrast, TGF-alpha was able to exert its mitogenic effects equally on b oth sides of the cell monolayer independent of its polarized disruptio n of tight junction formation, Our results represent the first evidenc e for a functional polarization of the epidermal growth factor recepto r and strongly implicate the glucocorticoid-regulated formation of tig ht junctions in policing the polarized responsiveness of mammary cells to growth factors.