title: Differential regulation of communication by retinoic acid in homologous and heterologous junctions between normal and transformed cells.
abstract: The permeability of junctions between cells of the same type (homologous junctions) is greatly increased by retinoic acid (10(-9)-10(-8) M), a probable morphogen, and this responsiveness is shared by a variety of normal and transformed cell types (Mehta, P.P., J.S. Bertram, and W.R. Loewenstein. 1989. J. Cell Biol. 108:1053-1065). Here we report that the heterologous junctions between the normal and transformed cells respond in the opposite direction; their permeability is reduced by retinoic acid (greater than or equal to 10(-9) M) and its benzoic acid derivative tetrahydrotetramethylnaphthalenylpropenylbenzoic acid (greater than or equal to 10(-11) M). The opposite responses of the two classes of junction are shown to be concurrent; in cocultures of normal 10T1/2 cells and their methylcholanthrene-transformed counterparts, the permeability of the heterologous junctions, which is lower than that of the homologous junctions to start with, falls (within 20 h of retinoid application), at the same time that the permeability of the homologous junctions rises in both cell types. Such a counter-regulation requires a minimum of three degrees of cellular differentiation. A model is proposed in which the differentiations reside in a trio of junctional channel protein. The principle of the model may have wide applications in the regulation of intercellular communication at tissue boundaries, including embryonic ones.
authors.affiliation: Department of Physiology and Biophysics, University of Miami School of Medicine, Florida 33101.
authors.forename: P P
authors.initials: PP
authors.lastname: Mehta
authors.forename: W R
authors.initials: WR
authors.lastname: Loewenstein
mesh_terms: D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D002461:Cell Line, Transformed; D002463:Cell Membrane Permeability; D007365:Intercellular Junctions / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D012176:Retinoids / Q000494:pharmacology; D015291:Transforming Growth Factors / Q000494:pharmacology; D014212:Tretinoin
chemical_list: D001565:Benzoates; D012176:Retinoids; D014212:Tretinoin; C038864:4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid; D015291:Transforming Growth Factors