Effects of retinoids and interferon‐gamma on cultured breast cancer cells in comparison with tumor necrosis factor alpha

Abstract

The combination of retinoic acid or tumor necrosis factor alpha (TNF‐alpha) with interferon gamma (IFN‐gamma) resulted in a synergistic amplification of the anti‐proliferative effect of IFN‐gamma on cultured breast cancer cells. Retinoic acid could be replaced by other biologically active retinoids. This synergism was also observed for the induction of 2′‐5′‐oligoac enylate‐synthetase, an enzyme which is not expressed constltutively on BT‐20 human breast cancer cells and not inductile by retinoic acid or TNF‐alpha alone. However, both substances augmented the IFN‐gamma‐mediated expression. On the other hand, only TNF‐alpha and not retinoic acid was able to increase the IFN‐gamma induced expression of HLA‐DR on the cell surface. Both cytokines antagonized the IFN‐gamma effect on detachability of cultured BT‐20 cells. The combinations of retinoic acid with IFN‐gamma increased the down‐regulation of specific binding sites for ¹²⁵ l‐IFN‐gamma. On the other hand, IFN‐gamma exerted no effect on the cancer traction of the cytoplasmic binding protein for retinoic acid. Data obtained in this study demonstrate a different patten of action between retinoic acid and TNF‐alpha regarding their synergism in combination with IFN‐gamma.