The combination of retinoic acid or tumor necrosis factor for TNF-alpha. IFN-gamma and TNF-alpha were diluted in alpha FNF-alpha) with interferon gamma (IFN-gamma) re-minimum essential medium (MEM) containing 15 % fetal bosulted in a Synergistic amplification Of the anti-proliferative vine Semm (FBS) and stored at -70°C until use. The retinoids effect of IFN-gamma on cultured breast cancer cells. Retinoic were donated by D ~. w. ~~l l ~~, Hoffmann-La Roche, acid could be replaced by other biologically active retinoids. Switzerland, and Dr, R. Moon, Illinois of Technol-This synergism was also observed for the induction of 2'-5'constitutively on BT-20 human breast cancer cells and not (1) all-tranS-retinOiC acid; (2) etretin (Ro 10-1670); (3) etretininducible by retinoic acid or TNF-alpha alone. However, both ate (Ro 10-9359); (4) 4-hydroxy-phenylretinamide; ( 5 ) p-((E)substances augmented the IFN-gamma-mediated expression. 2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl-l-pro-On the other hand, only TNF-alpha and not retinoic acid was peny1)benzoic acid (Ro 13-7410); (6) ethyl p-((E)-2-(5,6,7,8able to increase the IFN-gamma induced expression of HLA-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-1-propenyl)benzo-DR on the cell surface. Both cytokines antagonized the IFN-ate (Ro 13-6298); (7) @)-I, 2,3,4-tetrahydro-l, 1,4,4-tetracombinations of retinoic acid with IFN-gamma increased the formulae of the retinoids used are shown in Figures I and 2, down-regulation of specific binding sites for '251-IFN-gamma. On the other hand, IFN-gamma no effect on the For all experiments 1 mM ethanolic solutions were prepared concentration of the cytoplasmic binding protein for retinoic and further diluted in complete culture medium (Marth et acid. Data obtained in this study demonstrate a different a!., 1986). Cell culture pattern of action between retinoic acid and TNF-alpha regarding their synergism in combination with IFN-gamma. oligoadenylate-synthetase, an enzyme which is not expressed OgY, Chicago. In this study the following retinoids were used: gamma effect on detachability of cultured BT-20 cells. The methyl-6-(alpha-methylstyryl)naphthalene (Ro 15-0778). The